Fat Breakdown Research Articles

Intravenous Infusions of Glycerol Versus Propylene Glycol for the Regulation of Negative Energy Balance in Sheep: A Randomized Trial.

Simple SummaryPropylene glycol (PG) and glycerol are common energy substances used to supplement the feed of transitioning ruminants in order to minimize the development of metabolic disorders related to energy deficiency. Their effects on the energetic status of the animal have been, thus far, studied mostly by oral administration, which exposes them to substantial microbial metabolism in the rumen. This study compared the direct metabolic effects of these substances following their intravenous (IV) infusion. We found that glycerol was highly glucogenic and insulinotropic, as expected. However, surprisingly, PG had no significant effect on the circulating levels of glucose or insulin. Unlike glycerol, PG significantly raised circulating lactate levels and showed some potential tissue damage activity. Our study points to glycerol, rather than PG, as a potential IV treatment for efficient relief of hypoglycemia and hyperketonemia.Negative energy balance (NEB) is a state of insufficient dietary-energy consumption, characterized by the breakdown of adipose fat to meet the physiological energy expenditure. Extensive NEB, as common in high-yielding transitioning ruminants, drives significant metabolic disturbance and pathologies such as pregnancy toxemia and ketosis. Strategies to minimize the severity of NEB include the use of energy-dense feed supplements, like glycerol and propylene glycol (PG), or IV glucose infusion during severe hypoglycemia. PG and glycerol have been studied mainly by oral or ruminal administration, which exposes them to substantial metabolism in the digestive system. To investigate their direct benefits to mitigating NEB, we intravenously infused them into sheep induced into NEB by feed restriction. Sixteen 5-month-old ewe lambs at NEB were IV-treated with 170 mL isotonic saline containing 15% glycerol or 15% PG. Both PG and glycerol effectively reduced hyperketonemia by 57% and 61%, and inhibited adipose lipolysis by 73.6% and 73.3%, respectively. Surprisingly, only glycerol was glucogenic (p < 0.0001) and insulinotropic (p < 0.0075), while PG was primarily utilized for production of lactate (p < 0.0001). Tissue-damage biomarkers indicated hemolytic activity for PG. This study revealed glycerol as a superior IV treatment for effective relief of NEB. Since it carries no risk of glucose overloading, glycerol IV infusion may also have clinical advantages over glucose for treatment of pregnancy toxemia and ketosis.

Fat Embolism, Fat Embolism Syndrome and the Autopsy.

Fat embolism is common following trauma and is a common autopsy finding in these cases. It may also be seen in non-traumatic cases and is seen in children as well as adults. In comparison fat embolism syndrome (FES) only occurs in a small number of trauma and non-trauma cases. Clinical diagnosis is based on characteristic clinical and laboratory findings. Fat embolism exerts its effect by mechanical blockage of vessels and/or by biochemical means including breakdown of fat to free fatty acids causing an inflammatory response. Fat embolism can be identified at autopsy on microscopy of the lungs using fat stains conducted on frozen tissue, including on formalin fixed but not processed tissue. With FES fat emboli can be seen in other organs including the brain, kidney and myocardium. Fat can also be identified with post-fixation staining, typically with osmium tetroxide. Scoring systems have been developed to try and determine the severity of fat embolism in lung tissue. Fat embolism is also common following resuscitation. When no resuscitation has taken place, the presence of fat on lung histology has been used as proof of vitality. Diagnosis of fat embolism syndrome at autopsy requires analysis of the history, clinical and laboratory findings along with autopsy investigations to determine its relevance, but is an important diagnosis to make which is not always identified clinically. This paper reviews the history, clinical and laboratory findings and diagnosis of fat embolism and fat embolism syndrome at autopsy.

P33. Degenerative paraspinal muscles impact thoracic spine compensation in ASD patients

BACKGROUND CONTEXT Flattening of the thoracic spine is a common biomechanical compensatory mechanism for adult spinal deformity (ASD). The literature shows that younger ASD patients recruit more thoracic flattening than older patients. It is hypothesized that differences in muscle quality between younger and older ASD patients explains this difference in the recruitment of thoracic compensation. PURPOSE Investigate the relationship between paraspinal muscle degeneration and recruitment of thoracic compensation. STUDY DESIGN/SETTING Retrospective review of a prospective database. PATIENT SAMPLE ASD patients from a prospective database. OUTCOME MEASURES Posterior paraspinal muscle fat infiltration, thoracic kyphosis between T4 and T12 (TK) and pelvic retroversion (PT). METHODS ASD patients with spino-pelvic deformity (defined as SRS-Schwab PI-LL modifier of + or ++) and available pre-op CT imaging were identified from a retrospective database. Patients with previous fusion of the thoracic spine were excluded. Erector spinae and multifidus measurements were manually contoured on CT imagesat three vertebral levels (T2, T10, and L3), at three locations per level: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Fat infiltration (Fat) within each muscle was defined as the number of voxels with a Hounsfield unit (HU) corresponding to fat (-190 to 0) divided by the total number of voxels. The maximum fat infiltration (MaxFat) was determined by taking the muscle with the highest percentage of Fat. After a Pearson correlation analysis, the cohort was separated into 2 groups: high Fat (HFat) and Low Fat (LFat) based on MaxFat threshold of 35%. Demographics and radiographic parameters including TK and PT were compared between groups. RESULTS Of the 57 patients (mean age 61 yrs, 75% F, BMI 28) that met inclusion, 26% had a fused lumbar spine. Assessed by +/++ SRS-Schwab modifiers, 90% of patients had severe PT malalignment and 75% a severe SVA malalignment. Breakdown of Fat and area by vertebral level was: T2 (35% and 1332mm²), T10 (30% and 1910mm²), L3 (38% and 3915mm²). TK correlated significantly with Fat at all levels from T2 to L3 (r=-0.498, r=-0.519, r=-0.472), FatMax (r=-0.470) and area at T10 (r=-0.341). PT correlated significantly with FatMax (r=0.333) and T10 Fat(r=0.548). After grouping, 31 pts were HFat, and 25 pts were LFat. HFat pts were older (64.2 vs 56.3, p=0.047) and had a greater BMI (30.1 vs 25, p=0.002). The groups did not differ in sex or rates of lumbar fusion. In terms of spinal alignment, HFat pts had a higher T1 pelvic angle (30.7° vs 23.7°), a higher TK (-34.6° vs -22.9°), and a higher PT (30.1° vs 25.2°), without difference in lumbar deformity or other sagittal parameters. CONCLUSIONS Patients with higher fat infiltration in paraspinal muscles show less compensation with the thoracic spine than patients with leaner musculature, despite having similar lumbar deformities. Consequently, patients with degenerative paraspinal musculature have more pelvic retroversion, causing greater gait disruption due to limitation in hip extension. The assessment of fatty infiltration in posterior paraspinal muscles could help identify patient compensatory profile and aid in surgical planning. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

SENYAWA KUERSETIN SEBAGAI AGEN ANTIKANKER KOLOREKTAL SECARA IN SILICO

Colorectal cancer is a third rank malignant cancer in Indonesia, generally caused by the diet of the Indonesian people who have change with the consumption of food with high fat and low in fiber, also due to the production of carcinogenic substances from the breakdown of fat. In the condition of colorectal cancer there is overexpression of COX-2 and inhibition of Caspase-3 which causes the increase of cancer cells survival and causes inhibition of apoptosis mechanism. Quercetin is one of flavonoid which known have activity as an antitumor and tested in vitro can induce apoptosis on WiDr colorectal cancer cells . The purpose of this study was to determine the affinity and mechanism of quercetin compounds on COX-2 and Caspase-3 target proteins as colorectal anticancer by in silico with molecular docking. The study was conducted exploratively with the stages of preparing a database of 3D quercetin structures, as well as COX-2 and Caspase-3 proteins, optimization of 3D quercetin structure, protein preparation, molecular docking method validation, and quercetin docking on these proteins. Docking results were assessed from the binding energy and hydrogen bonds that formed between quercetin with proteins. The smaller binding energy value, the stronger the bond between quercetin and proteins is. The results showed that quercetin had an activity as a colorectal anticancer because it was able to inhibit COX-2 and induce Caspase-3 with binding energy values of -9.54 and -4.59. These results showed that quercetin has the potential to induce apoptosis in colorectal cancer. &#x0D; Keywords: colorectal cancer, quercetin, caspase-3, in silico

HNF1α Controls Liver Lipid Metabolism and Insulin Resistance via Negatively Regulating the SOCS-3-STAT3 Signaling Pathway.

This study is aimed at evaluating the effects, functions, and mechanism of HNF1α on hepatic glycolipid metabolism. In this study, free fatty acid- (FFA-) induced steatosis of hepatocyte liver cell LO2 was used as an in vitro model. The methods of Oil Red O staining, RT-qPCR, western blot, and immunofluorescence staining were used to detect LO2-regulated HNF1α expression and its effects on FFA-induced LO2 cell steatosis, the insulin signaling and SOCS-3-STAT3 signaling pathways, the expression of lipid metabolism-related regulators, and phosphorylation. With increased FFA induction time, the expression of HNF1α in the LO2 fatty degeneration hepatic cells gradually decreased. Downregulation of HNF1α expression aggravated FFA-induced steatosis of LO2 hepatocytes. HNF1α promotes activation of the insulin pathway and oxidative breakdown of fat and inhibits lipid anabolism. Inhibitors of STAT3 can reverse the regulation of decreased HNF1α expression on the insulin signaling pathway and fat metabolism. We also confirmed this pathway using HNF1α-/- mice combining treatment with STAT3 inhibitor NSC 74859 in vivo. HNF1α regulates hepatic lipid metabolism by promoting the expression of SOCS-3 and negatively regulating the STAT3 signaling pathway.

Differential Effects of a Bout of Moderate‐intensity Physical Exercise on Adipose Tissue Inflammation in Lean and in Obese Mice

Inflammation is an adaptive response that is triggered by the noxious stimuli in order to maintain the homeostasis. Previous studies have shown that higher lipolysis rate after fasting is associated with the influx of leukocytes and increased cytokine levels in the epididymal adipose tissue (EAT). Fat mobilization is also highly activated during and post‐exercise. In spite of substantial evidences having supported the link between inflammation and exercise, the association between EAT, cytokines and acute exercise is less explored. Herein, we characterized the EAT inflammation following exercise in lean and obese mice. We used in vivo confocal imaging from EAT vessel to display the higher recruitment of neutrophils 0 and 6 hours post‐exercise in lean mice. Additionally, we found that exercise enhanced the levels of IL‐6 and TNF‐alpha in the EAT which were correlated with increased serum free fatty acids in lean mice. Interestingly, obese mice subjected to exercise showed lower pro‐inflammatory level of cytokines in the EAT and lost the correlation between IL‐6, TNF‐alpha and free fatty acids. Furthermore, obese mice increased IL‐10 24h post‐exercise. Together, our data show that exercise induces inflammation in the EAT in lean mice. These responses may have a physiological purpose and be important to stimulate fat breakdown. Conversely, exercise in obese mice promoted a reduction in pro‐inflammatory mediators and elevated IL‐10. Despite of the low‐grade inflammation being associated with metabolic dysfunctions, at least in part, the inflammatory milieu in EAT may be also important to regulate fat remodeling induced by exercise.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Lipid Metabolism at Two Different Walking Speeds in Obese Individuals: Pilot Study

Exercise is an important factor of obesity and overweight management. American College of Sports Medicine recommends that 150–250 minutes per week and up to 60 minutes per day of moderate‐intensity aerobic exercise should be performed for weight gain prevention or modest weight reduction. Walking is a common and relatively safe form of aerobic exercise that can easily be incorporated into weight management programs. The energy expenditure associated with walking has been reported to be either linearly or slightly exponentially related to speed. Thus, interval walking training has been developed as a novel free‐living training modality that improves physical fitness and cardiovascular risk factors in humans.PURPOSEto determine if an interval walking exercise increases fat breakdown, fat utilization, and energy expenditure to a greater extent, compared with constant walking exercise in obese adults.METHODSThis study was set as randomized crossover design. Six sedentary obese individuals (BMI ≥ 30 kg/m2 and 18–50 yrs) were recruited. Initially six subjects were randomly assigned into a constant speed walking group (CON) or an interval walking group (INT). Then, CON became INT and INT became CON. The constant speed walking consists of a single bout of 40 min walking exercise at 45% of VO2max on a treadmill. The interval walking consists of a single bout of 40 min walking exercise with cycles of alternating 3‐min slow (30% of VO2max), 3‐min moderate (45% of VO2max), and 3‐min fast (60% of VO2max) walking. Energy expenditure and fat usage were measured at rest and every 10min during walking exercises via indirect calorimetry. Blood samples were drawn at rest and every 10min during walking exercises to measure glycerol levels. Two‐way ANOVA was used to determine differences in energy expenditure and fat utilization between the groups.RESULTSThe net rates of fat utilization (g/min) and calorie expenditure (kcal/min) were not different between the groups during walking exercises. Also, blood glycerol concentrations were not different between the groups at any time points of exercise. However, the net rates of fat utilization, calorie expenditure, and blood glycerol concentrations were significantly higher at 30min and 40min of exercise, compared to those at 10min of exercise in both groups.CONCLUSIONOur data show that walking speeds might not be a primary factor to regulate fat utilization and energy expenditure during low and moderate exercise intensities. However, an increase in fat metabolism and energy expenditure during walking exercises may be attributed to the longer duration of exercise. Thus, these findings may provide a better exercise strategy to increase lipid breakdown and prevent weight gain in overweight/obese people.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of liver fatty acid binding protein (L-FABP) gene ablation on lipid metabolism in high glucose diet (HGD) pair-fed mice

Liver fatty acid binding protein (L-FABP) is the major fatty acid binding/”chaperone” protein in hepatic cytosol. Although fatty acids can be derived from the breakdown of dietary fat and glucose, relatively little is known regarding the impact of L-FABP on phenotype in the context of high dietary glucose. Potential impact was examined in wild-type (WT) and Lfabp gene ablated (LKO) female mice fed either a control or pair-fed high glucose diet (HGD). WT mice fed HGD alone exhibited decreased whole body weight gain and weight gain/kcal food consumed—both as reduced lean tissue mass (LTM) and fat tissue mass (FTM). Conversely, LKO alone increased weight gain, lean tissue mass, and fat tissue mass while decreasing serum β-hydroxybutyrate (indicative of hepatic fatty acid oxidation)—regardless of diet. Both LKO alone and HGD alone significantly altered the serum lipoprotein profile and increased triacylglycerol (TG), but in HGD mice the LKO did not further exacerbate serum TG content. HGD had little effect on hepatic lipid composition in WT mice, but prevented the LKO-induced selective increase in hepatic phospholipid, free-cholesterol and cholesteryl-ester. Taken together, these findings suggest that high glucose diet diminished the effects of LKO on the whole body and lipid phenotype of these mice.

Evaluation of Liraglutide Effect on Serum Adipocytokines of Adults Male Wistar Rats with Insulin Resistance That Induced by High Fat Diet

Insulin resistance (IR) is the state in which insulin-stimulated glucose uptake is blunted in the insulin sensitive-tissue leading to state of prediabetes and T2DM, IR characterized by hyperglycemia and hyperinsulinemia in the fasting state, elevated glycosylated hemoglobin (HbA1c) level, hyperlipidemia, postprandial hyperglycemia, elevated plasma levels of pro-inflammatory markers and hypoadiponectinemia. Type 2 diabetes mellitus reported with peripheral insulin resistance (IR) and reduced production of insulin from pancreatic β-cells, IR elevates plasma fatty acids, decreasing glucose transportation to muscles and increased breakdown of fat finally leads to increased glucose production from the liver. This study was designed to evaluate the effect of liraglutide on serum adipocytokines of adult male rats with insulin resistance that induced by high fat diet, Chronic high fats diet feeding is a common cause of disturbing leptin signaling in hypothalamus leading to the state of hyperphagic obesity and leptin resistance. Liraglutide improve meal-stimulated insulin secretion so it's called incretin mimetic. It is glucagon like peptide-1 receptor agonist that adjust weight loss and glucose control via glucagon like peptide-1 receptors in the central nervous system or indirectly through activation of peripheral neurons. Current study utilized thirty-six adult male wistar rats (weighing 200-220gm), they were divided into two main groups: normal diet group (group A) that includes 12 rats receiving normal pellets and high fat diet group (group B and C) which has 24 rats feeding high fat diet pellets. Animals fed high fat diet pellets for 8 weeks to induce insulin resistance were divided into two groups: Group B received high fat diet pellets for 8 weeks then administered 0.5ml/kg normal saline intraperitoneal for four weeks. Group C received high fat diet pellets for 8 weeks then received 600μg/kg/day intraperitoneal liraglutide +0.5ml/kg normal saline four weeks along with high fat diet. High fat diet pellets caused a significant increase in body weight and blood glucose of high fat diet group. Liraglutide revealed a significant elevation in serum level of anti-inflammatory adipokines of group C. It also produces a significant reduction in serum level of pro-inflammatory cytokines of group C when compared with group B and control group. As conclusion, anti-inflammatory effects of liraglutide significantly elevate serum level of anti-inflammatory cytokines as well as significantly reduce serum level of pro-inflammatory cytokines.

Evaluation of Liraglutide Effect on Serum Adipocytokines of Adults Male Wistar Rats with Insulin Resistance That Induced by High Fat Diet

Insulin resistance (IR) is the state in which insulin-stimulated glucose uptake is blunted in the insulin sensitive-tissue leading to state of prediabetes and T2DM, IR characterized by hyperglycemia and hyperinsulinemia in the fasting state, elevated glycosylated hemoglobin (HbA1c) level, hyperlipidemia, postprandial hyperglycemia, elevated plasma levels of pro-inflammatory markers and hypoadiponectinemia.&#x0D; Type 2 diabetes mellitus reported with peripheral insulin resistance (IR) and reduced production of insulin from pancreatic β-cells, IR elevates plasma fatty acids, decreasing glucose transportation to muscles and increased breakdown of fat finally leads to increased glucose production from the liver.&#x0D; This study was designed to evaluate the effect of liraglutide on serum adipocytokines of adult male rats with insulin resistance that induced by high fat diet, Chronic high fats diet feeding is a common cause of disturbing leptin signaling in hypothalamus leading to the state of hyperphagic obesity and leptin resistance. Liraglutide improve meal-stimulated insulin secretion so it's called incretin mimetic. It is glucagon like peptide-1 receptor agonist that adjust weight loss and glucose control via glucagon like peptide-1 receptors in the central nervous system or indirectly through activation of peripheral neurons.&#x0D; Current study utilized thirty-six adult male wistar rats (weighing 200-220gm), they were divided into two main groups: normal diet group (group A) that includes 12 rats receiving normal pellets and high fat diet group (group B and C) which has 24 rats feeding high fat diet pellets. Animals fed high fat diet pellets for 8 weeks to induce insulin resistance were divided into two groups: Group B received high fat diet pellets for 8 weeks then administered 0.5ml/kg normal saline intraperitoneal for four weeks. Group C received high fat diet pellets for 8 weeks then received 600μg/kg/day intraperitoneal liraglutide +0.5ml/kg normal saline four weeks along with high fat diet.&#x0D; High fat diet pellets caused a significant increase in body weight and blood glucose of high fat diet group. Liraglutide revealed a significant elevation in serum level of anti-inflammatory adipokines of group C. It also produces a significant reduction in serum level of pro-inflammatory cytokines of group C when compared with group B and control group.&#x0D; As conclusion, anti-inflammatory effects of liraglutide significantly elevate serum level of anti-inflammatory cytokines as well as significantly reduce serum level of pro-inflammatory cytokines.

Triacylglycerol Metabolism in Drosophila melanogaster.

Triacylglycerol (TAG) is the most important caloric source with respect to energy homeostasis in animals. In addition to its evolutionarily conserved importance as an energy source, TAG turnover is crucial to the metabolism of structural and signaling lipids. These neutral lipids are also key players in development and disease. Here, we review the metabolism of TAG in the Drosophila model system. Recently, the fruit fly has attracted renewed attention in research due to the unique experimental approaches it affords in studying the tissue-autonomous and interorgan regulation of lipid metabolism in vivo Following an overview of the systemic control of fly body fat stores, we will cover lipid anabolic, enzymatic, and regulatory processes, which begin with the dietary lipid breakdown and de novo lipogenesis that results in lipid droplet storage. Next, we focus on lipolytic processes, which mobilize storage TAG to make it metabolically accessible as either an energy source or as a building block for biosynthesis of other lipid classes. Since the buildup and breakdown of fat involves various organs, we highlight avenues of lipid transport, which are at the heart of functional integration of organismic lipid metabolism. Finally, we draw attention to some "missing links" in basic neutral lipid metabolism and conclude with a perspective on how fly research can be exploited to study functional metabolic roles of diverse lipids.

PO-287 Application of low-load blood flow restriction training in elderly chronic diseases

Objective Low-load blood flow restriction training (It's also called KAATSU) refers to the stimulation of skeletal muscle growth and muscle strength with low-load training intensity when the blood flow of the proximal venous vessels of the limbs is restricted for a short time. Thereby improving the muscle function of the skeletal muscle. KAATSU uses a low training load (20% IRM), which can play a medium to high load training effect. It is suitable for older people with weaker constitution, less skeletal muscle strength, and different degrees of aging muscle loss (sarcopenia). Therefore, there have been more and more studies on KAATSU intervention in chronic diseases in the elderly in recent years. This study systematically reviews the recent progress in the application of KAATSU in chronic diseases in the elderly, and provides a theoretical basis for the widespread application of KAATSU in the intervention of chronic diseases in the elderly. &#x0D; Methods Enter keywords in the websites of CNKI, CQVIP, Elsevier Science Direct, and Journals @Ovid Full Text, Pub Met, etc: “KAATSU, chronic disease”/“blood flow restriction, older”, a total of more than 3000 articles were searched, Screening of 98, At last, more than 40 literatures meeting the standards were analyzed and summarized.&#x0D; Results 1) Applied to skeletal muscle atrophy: KAATSU can significantly increase the cross-sectional area of skeletal muscle muscles, strengthen muscle strength, improve muscle contraction function, effectively prevent and interfere with sarcopenia, Especially for stroke patients with rehabilitation and long-term bed caused by muscular atrophy of disuse has a good clinical effect.2) Application to osteoporosis: KAATSU can improve bone mineral density, stimulate bone cell activity and improve bone health, but it is not yet certain whether to improve Senile osteoporosis. Future research should be combined with nutritional supplements to comprehensively evaluate its therapeutic effect. 3) Applied to cardiovascular and cerebrovascular diseases: Long-term KAATSU can effectively improve blood lipid metabolism, optimize cardiovascular function parameters, It doesn't activate the thrombin system, and has no significant negative impact on cardiovascular function in the elderly, the application effect is good in cardiovascular and cerebrovascular diseases such as atherosclerosis and hypertension.4) Application to metabolic syndrome: KAATSU can promote fat breakdown, reduce BMI,body fat percentage, insulin resistance index, glycosylated hemoglobin index, and improve diabetes and senile obesity in the elderly. 5) Others: There are a few studies showing that KAATSU can improve the daily activities of patients with Alzheimer's disease, promote the remodeling of bone tissue in elderly patients with osteonecrosis, and intervene with the muscle atrophy of patients with certain chronic heart diseases. &#x0D; Conclusions KAATSU is an effective exercise method for the elderly and has a good application prospect in comprehensive prevention and intervention of chronic diseases in the elderly. It deserves popularization and application. Future research could try to used in chronic diseases such as chronic obstructive pulmonary disease and senile osteoarthritis.

Evaluation of Diagnosis and Management Plan of Diabetes Mellitus Related Cystic Fibrosis in Children

Background: Cystic fibrosis (CF) is a disease that occurs as a result of genetic mutations in cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR can be found in airways epithelial cells, intestine and cells with exocrine and exocrine function. CF is associated with variant complications, Cystic Fibrosis-Related Diabetes (CFRD) is considered as one of the most common complications of CF. Objective: In this review, we discussed the recent updates about Cystic Fibrosis-Related Diabetes (CFRD) diagnosis and management plan. Methods: PubMed database were used for articles selection. All relevant articles related to our review were chosen to cover the following topics: Cystic Fibrosis, Cystic Fibrosis Related Diabetes management, Cystic Fibrosis Related Diabetes diagnosis. We excluded other articles, which are not related to our objectives. Conclusion: CFRD can significantly worse the health condition of CF patients. However, with the recent advancement of management plans of CFRD, previous sex differences in mortality have disappeared and that the gap in mortality between CF patients with diabetes and CF patients without diabetes has considerably narrowed. Early diagnosis and early intervention also helped in improving the quality of CFRD patients and preventing the complications. This can be obtained by annual screening for DM among CF patients since 10 years of age using OGTT as recommended by ADA. The primary pathologic feature of CFRD is insulin insufficiency. It leads to increased breakdown of protein and fat. So, insulin replacement is the only recommended medical treatment and it has been shown to improve clinical outcomes. Oral diabetes agents are usually not recommended in CFRD.

Evaluation of Diagnosis and Management Plan of Diabetes Mellitus Related Cystic Fibrosis in Children

Background: Cystic fibrosis (CF) is a disease that occurs as a result of genetic mutations in cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR can be found in airways epithelial cells, intestine and cells with exocrine and exocrine function. CF is associated with variant complications, Cystic Fibrosis-Related Diabetes (CFRD) is considered as one of the most common complications of CF. Objective: In this review, we discussed the recent updates about Cystic Fibrosis-Related Diabetes (CFRD) diagnosis and management plan. Methods: PubMed database were used for articles selection. All relevant articles related to our review were chosen to cover the following topics: Cystic Fibrosis, Cystic Fibrosis Related Diabetes management, Cystic Fibrosis Related Diabetes diagnosis. We excluded other articles, which are not related to our objectives. Conclusion: CFRD can significantly worse the health condition of CF patients. However, with the recent advancement of management plans of CFRD, previous sex differences in mortality have disappeared and that the gap in mortality between CF patients with diabetes and CF patients without diabetes has considerably narrowed. Early diagnosis and early intervention also helped in improving the quality of CFRD patients and preventing the complications. This can be obtained by annual screening for DM among CF patients since 10 years of age using OGTT as recommended by ADA. The primary pathologic feature of CFRD is insulin insufficiency. It leads to increased breakdown of protein and fat. So, insulin replacement is the only recommended medical treatment and it has been shown to improve clinical outcomes. Oral diabetes agents are usually not recommended in CFRD.

Ghrelin Directly Stimulates Fatty Acid Oxidation in Skeletal Muscle

Ghrelin is classically known as a central appetite stimulating hormone, but has recently been recognized to have a significant role in peripheral tissue energy metabolism. Given that ghrelin rapidly increases prior to entrained mealtimes, it is possible that ghrelin may act as part of a preparatory response to facilitate the metabolism of ingested glucose and lipids. Skeletal muscle is a major site for glucose and lipid disposal; however, the direct effects of ghrelin on this tissue remain understudied. Furthermore, studies examining the metabolic effects of in vivo ghrelin injections fail to distinguish independent effects of ghrelin from secondary effects such as increases in growth hormone. Therefore, the purpose of this study was to determine the direct effects of the two main isoforms of ghrelin, acylated (AG) and unacylated (UnAG) on fatty acid (FA) metabolism in isolated rat skeletal muscle. Specifically, we examined the effect of ghrelin (AG, UnAG) on labeled palmitate oxidation and incorporation into major lipid pools (diacylglycerol, DAG; triacylglycerol, TAG) under conditions of low glucose (5 mM) or high glucose concentrations (10 mM). Soleus (SOL) and extensor digitorum longus (EDL) were used as representative oxidative and glycolytic muscles and 1mM palmitate was used in the medium throughout. We hypothesized that ghrelin would facilitate the uptake of fatty acids into skeletal muscle thereby increasing oxidation and incorporation into lipid pools. SOL and EDL muscle strips were excised from male Sprague‐Dawley rats (~250 g) and incubated with either 150 ng/ml of AG or UnAG, or 2 mM of 5‐Aminoimidazole‐4‐carboxamide ribonucleotide (AICAR), a known stimulant of fatty acid oxidation (positive control). To assess oxidation, sulfuric acid was added directly to the medium containing the muscle to release14CO2, which was trapped in a suspended vial containing benzethonium hydroxide. In a separate set of experiments, 14C palmitate incorporation into muscle lipid pools was assessed by extracting lipids into a 2:1 chloroform:methanol solution and spotting on a thin layer chromatography plate. A repeated measures one‐way ANOVA uncorrected for Fisher's LSD was performed and significance was accepted at p≤0.05. In agreement with our hypothesis, both isoforms of ghrelin (AG and UnAG) stimulated palmitate oxidation. At 10 mM glucose, both AG and UnAG increased palmitate oxidation (~40%; p&lt;0.05) in SOL and EDL. At the lower glucose concentration (5 mM), UnAG increased palmitate oxidation (SOL, 41%; EDL, 27%; p&lt;0.05); and a near significant trend of AG induced FA oxidation was observed in EDL (23%; p=0.07), but not in SOL (14%, p=0.258). Deposition of labeled fatty acids into DAG and TAG pools was unaffected by AG and UnAG, suggesting that the acute effect of ghrelin on muscle is solely directed at oxidation. In summary, ghrelin has a direct, acute stimulatory effect on fatty acid metabolism in both oxidative and glycolytic skeletal muscle. This effect appears to be directed only at oxidation, and occurs regardless of the glucose environment. Further experiments will be performed to assess the effect of ghrelin on fat breakdown (lipolysis) in muscle and the underlying cellular signaling mechanisms involved.Support or Funding InformationNSERCThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

O10.6. OLANZAPINE IMPAIRS CENTRAL INSULIN ACTION: EFFECTS ON BODY FUEL PREFERENCE IN RATS

BackgroundAntipsychotics (APs) remain the cornerstone of treatment in schizophrenia, with increasing use on- and off- label. Olanzapine (OLZ) is a highly prescribed, high metabolic liability AP. Olanzapine has also been found to shift major fuel preference from carbohydrates to fats (while impairing fat breakdown and decreasing availability of fat as a substrate). The shift toward fat utilization is demonstrated by decreases in respiratory exchange ratio (RER). Notably, APs may alter signaling pathways in insulin-sensitive brain areas, particularly in the hypothalamus, that play a role glucose regulation and energy expenditure.MethodsWe investigated the effects of intracerebroventricular (ICV) insulin administration on OLZ-induced disruptions in energy homeostasis. Male Sprague Dawley rats were assigned to 4 treatment groups (ICV-peripheral): Vehicle (VEH)-VEH (n = 5), Insulin (INS)-VEH (n = 7), INS-OLZ (n = 6), VEH-OLZ (n = 5). Following acclimatization to the metabolic cages, rats received injections of INS (10mU) or VEH into the 3rd ventricle, and OLA (3mg/kg) or VEH subcutaneously at the beginning of the light (7AM, t=0) and dark (7PM, t=12h) cycle. Dose of OLZ was chosen based on clinically relevant >65% dopamine (D2) brain occupancy. Dose of ICV insulin was chosen based on established decreases in food intake. Indirect calorimetry was used to calculate RER, and heat production. Cumulative food intake was measured at 12-hour intervals (t=12h and 24 h).ResultsTreatment with OLZ reproduced the previously established downward shift in RER during the dark phase (p=0.016), which occurred independently of changes in food intake or heat production. Central insulin also decreased RER (p=0.013), an unexpected finding as insulin has been associated with increased carbohydrate oxidation. This may have been secondary to decreased food intake associated with central INS (p=0.011), leading to a shift towards fat-oxidation characteristic of fasting. Co-administration of OLZ with central INS (INS-OLZ) abolished the treatment effect seen in the INS-VEH group relative to VEH-OLZ, shifting the RER profile to become similar to the VEH-OLZ group. Similarly, when OLZ was co-administered with ICV-INS, the effect of central INS to reduce food-intake was lost. An interaction effect (p=0.007) was observed between central insulin and subcutaneous OLZ treatments on RER, supporting the notion that these compounds may work through independent mechanisms to influence fuel preference.DiscussionTaken together, these findings suggest that: 1) central insulin stimulation alters metabolism but is unable to modulate OLZ-specific associated changes in RER; 2) this is likely occurring due to rapid induction of central insulin resistance by OLZ. Our data thus warrants further investigation into the effects of APs on central insulin sensing, and mitigation strategies (i.e. use of central insulin sensitizers) with the goal of mitigating the metabolic burden of these compounds.

Application of Various Techniques for Meat Preservation

Since the pre-historic times, meat is consumed by humans as part of diet. Meat is an animal flesh that is considered as an excellent source of high biological value protein, zinc, iron, magnesium, selenium, phosphorus, and vitamins. In recent years, global meat production and consumption have increased. The production of meat in the world was estimated at 317.17 million tons in 2016. Meat is very much susceptible to spoilage due to chemical and enzymatic activities.The breakdown of fat, protein, and carbohydrates of meat result in the development of off-odors, off-flavor and slim formation, which make the meat objectionable for the human consumption. Several factors such as moisture, light, microbes, atmospheric oxygen, temperature, and endogenous enzymes influence the freshness and shelf life of meat. Microbes are ubiquitous in distribution and can reach the meat from different sources thus causing its spoilage. Therefore, various technologies are used to preserve the meat in order to inactivate/destroy the microbes, which are implicated in foodborne infections. Canned food stored in cool and dry place can last up to a year. Since preservation of meat by irradiation requires heavy investment, its commercial application is still in its infancy. It is emphasized that preservation of meat is imperative to prevent the occurrence of deteriorative changes brought by microbial, chemical and physical process. Further, well preserved meat can give protection against all hazards for a considerable time.

Blubber news: whale fat is active!

In the world of physiology, scientists use model organisms, such as fish, rats and mice, to study how the complex relationship between the body and its environment influences behaviour. Yet, few have the courage to tackle the challenges of working with the largest mammals on Earth. Undeterred, Hope Ball from University of Akron, USA, and her collaborators from several US institutions decided to investigate how bowhead whales (Balaena mysticetus) and belugas (Delphinapterus leucas) tackle the physical challenges of survival in the extreme environment of the Arctic Ocean and their lengthy migrations.Whales have a unique layer of tissue under their skin called blubber, which provides buoyancy and thermal insulation in cold waters in addition to allowing them to store large amounts of fat to fuel migration while fasting. Other animals that undergo long periods of fasting also possess a specialized protein hormone, called leptin, that varies seasonally to suppress appetite and stimulate fat breakdown when the animals have stopped feeding. While whales are known to produce leptin, little was known about production of the hormone and how the levels vary in these animals.Ball and her colleagues partnered with residents of several Inupiat settlements during their annual subsistence hunt, to collect blubber and tissue samples from bowhead and beluga juveniles and adults during the autumn migration and in the spring. In samples collected from the whales in the autumn – following an intense summer feeding period – the authors reported that leptin gene expression was approximately 10- to 50-fold higher than in the spring whales, suggesting that extreme seasonal variation in leptin plays a role in regulating fat breakdown during fasting periods. The authors also reported that the largest amount of leptin was found in the deepest layer of blubber, where fat is actively broken down for energy production when food is unavailable. This suggests that leptin levels, in addition to seasonal cues, may drive the whales’ migration to and from summer feeding grounds.To determine the influence of season on fat utilization, the authors analysed the activity of the enzymes that break down fat. They found that in the autumn, when the whales were well fed, the blubber was composed of large fat cells and the activity of these enzymes was low. However, in winter, following migration from cold waters back to summer feeding grounds, the blubber contained smaller fat cells and more connective tissue, and the activity of the enzymes that break down fat was high. This suggests that the whales break down fat to maintain the energy demands of the body when they migrate. In addition, Ball and colleagues reported low levels of leptin in juveniles, which were similar to those found in the spring fasting adults, suggesting that the metabolism of the young whales is low to minimize energy loss and it is directed at stimulating appetite to ensure maturation.It appears that these extreme seasonal and life stage variations in leptin levels are unique adaptations that Arctic whales have evolved to drive fat utilization, feeding behaviour and initiation of migration in cold waters. In whales, leptin controls appetite and fat breakdown, thus making blubber an active player in a whale's physiology.

Muscles in diabetes

Muscles in diabetes

Lipid metabolism in Rhodnius prolixus: Lessons from the genome

The kissing bug Rhodnius prolixus is both an important vector of Chagas' disease and an interesting model for investigation into the field of physiology, including lipid metabolism. The publication of this insect genome will bring a huge amount of new molecular biology data to be used in future experiments. Although this work represents a promising scenario, a preliminary analysis of the sequence data is necessary to identify and annotate the genes involved in lipid metabolism. Here, we used bioinformatics tools and gene expression analysis to explore genes from different genes families and pathways, including genes for fat breakdown, as lipases and phospholipases, and enzymes from β-oxidation, fatty acid metabolism, and acyl-CoA and glycerolipid synthesis. The R. prolixus genome encodes 31 putative lipase genes, including 21 neutral lipases and 5 acid lipases. The expression profiles of some of these genes were analyzed. We were able to identify nine phospholipase A2 genes. A variety of gene families that participate in fatty acid synthesis and modification were studied, including fatty acid synthase, elongase, desaturase and reductase. Concerning the synthesis of glycerolipids, we found a second isoform of glycerol-3-phosphate acyltransferase that was ubiquitously expressed throughout the organs. Finally, all genes involved in fatty acid β-oxidation were identified, but not a long-chain acyl-CoA dehydrogenase. These results provide fundamental data to be used in future research on insect lipid metabolism and its possible relevance to Chagas' disease transmission.