Higher Serum Free Fatty Acids Research Articles

Heat-killed Lactobacillus brevis KB290 attenuates visceral fat accumulation induced by high-fat diet in mice.

AimsThis study aimed to evaluate the anti‐adiposity effect of heat‐killed Lactobacillus brevis KB290 originating from traditional Japanese fermented pickles in mice fed a high‐fat diet (HFD).Methods and ResultsC57BL/6J mice were fed a normal‐fat diet, HFD or HFD supplemented with heat‐killed KB290 for 8 weeks. Epididymal and renal adipose tissue weights, as well as areas of epididymal adipocytes, were significantly lower in the mice fed a HFD supplemented with KB290 than in those fed an unsupplemented HFD. Mice whose diets were supplemented with KB290 had elevated adiponectin and β3‐adrenergic receptor expression in epididymal adipose tissue and an accompanying higher serum free fatty acid level. Furthermore, the HFD‐induced elevations in serum glucose, insulin and HOMA‐IR were significantly suppressed by dietary supplementation with KB290. Amplicon sequencing of 16S rRNA genes revealed that KB290 ingestion altered the composition of the intestinal microbiota.ConclusionsHeat‐killed L. brevis KB290 suppressed diet‐induced visceral fat accumulation and ameliorated diet‐induced metabolic symptoms and intestinal gut microbiota modifications, suggesting possibility of novel paraprobiotic.Significance and Impact of the StudyHeat‐killed L. brevis KB290 is useable as a material to develop functional foods that attenuate visceral fat accumulation.

Metformin alleviates hyperuricaemia-induced serum FFA elevation and insulin resistance by inhibiting adipocyte hypertrophy and reversing suppressed white adipose tissue beiging.

Hyperuricaemia (HUA) significantly increases the risk of metabolic syndrome and is strongly associated with the increased prevalence of high serum free fatty acids (FFAs) and insulin resistance. However, the underlying mechanisms are not well established, especially the effect of uric acid (UA) on adipose tissue, a vital organ in regulating whole-body energy and FFA homeostasis. In the present study, we noticed that adipocytes from the white adipose tissue of patients with HUA were hypertrophied and had decreased UCP1 expression. To test the effects of UA on adipose tissue, we built both in vitro and in vivo HUA models and elucidated that a high level of UA could induce hypertrophy of adipocytes, inhibit their hyperplasia and reduce their beige-like characteristics. According to mRNA-sequencing analysis, UA significantly decreased the expression of leptin in adipocytes, which was closely related to fatty acid metabolism and the AMPK signalling pathway, as indicated by KEGG pathway analysis. Moreover, lowering UA using benzbromarone (a uricosuric agent) or metformin-induced activation of AMPK expression significantly attenuated UA-induced FFA metabolism impairment and adipose beiging suppression, which subsequently alleviated serum FFA elevation and insulin resistance in HUA mice. Taken together, these observations confirm that UA is involved in the aetiology of metabolic abnormalities in adipose tissue by regulating leptin-AMPK pathway, and metformin could lessen HUA-induced serum FFA elevation and insulin resistance by improving adipose tissue function via AMPK activation. Therefore, metformin could represent a novel treatment strategy for HUA-related metabolic disorders.

Metformin Alleviates Hyperuricemia-Induced Serum Free Fatty Acid Elevation and Insulin Resistance by Improving Adipose Tissue Function

Background: Hyperuricemia (HUA) significantly increases risk of metabolic syndrome, and is strongly associated with the increased prevalence of high serum free fatty acids (FFA) and insulin resistance. However, the detailed mechanism remains unclear. Adipose tissue plays a crucial role in FFA metabolism. In this study, we aimed to explore the effects and underlying mechanism of uric acid (UA) on the metabolic function of adipocytes. Further, we investigated whether the administration of metformin could alleviate HUA-related metabolic disorders Methods: We performed H&E and immunohistochemistry to analyze adipose tissues of normal and HUA patients. Then mRNA microarray analysis was used to compare mRNA expression profiles of 3T3-L1 cells with and without UA. HUA mice were treated with UA lowering agent (benzbromarone) and metformin, respectively, and then epididymal white adipose tissue (eWAT) were isolated for in vitro experiment. Fundings: UA induced adipocyte hypertrophy, inhibited hyperplasia and reduced its beige-like characteristics. The mRNA microarray data indicated that UA significantly decreased the expression of leptin, which was closely related to FFA metabolism and 5-AMP-activated protein kinase (AMPK) signaling pathway according to KEGG pathway analysis. Moreover, benzbromarone and metformin induced activation of AMPK expression significantly attenuated UA-induced FFA metabolism impairment and adipose beiging depression, which subsequently alleviated serum FFA elevation and insulin resistance in HUA mice. Interpretation: UA is involved in the etiology of serum FFA elevation and insulin resistance by impairing adipose tissue function, which is mediated by leptin-AMPK pathway. AMPK activation by metformin represents a novel potential treatment strategy for HUA-related metabolic disorders. Funding Statement: This project was supported by grants from National Nature Scientific Foundation of China (No.81830012, No.81670297). Doctoral Fund of Ministry of Education of Heilongjiang Province (LBH-Z17180) and Harbin Medical University Science Innovation Foundation (YJSKYCX2018-91HYD) also provided additional support. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Clinical sampling was approved by the Ethical Committee of First Affiliated Hospital of Harbin Medical University. The Animal Care and Use Committee of the First Affiliated Hospital of Harbin Medical University approved all protocols.

LncRNA LEGLTBC Functions as a ceRNA to Antagonize the Effects of miR-34a on the Downregulation of SIRT1 in Glucolipotoxicity-Induced INS-1 Beta Cell Oxidative Stress and Apoptosis.

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose and/or high serum free fatty acids. Chronic hyperlipidemia causes the dysfunction of pancreatic beta cells, which is aggravated in the presence of hyperglycemia (glucolipotoxicity). Long noncoding RNAs (lncRNAs) have been suggested to play key roles in type 1 diabetes mellitus development. However, their roles in glucolipotoxicity-induced beta cell dysfunction are not fully understood. In the present study, we identified the differentially expressed lncRNAs in INS-1 cells exposed to high glucose and palmitate (HG/PA). Among the dysregulated lncRNAs, NONRATT003679.2 (low expression in glucolipotoxicity-treated beta cells (LEGLTBC)) was involved in glucolipotoxicity-evoked rat islet beta cell damage. LEGLTBC functioned as a molecular sponge of miR-34a in INS-1 cells. Additionally, SIRT1 was identified as a target of miR-34a and LEGLTBC promoted SIRT1 expression by sponging miR-34a. The upregulation of LEGLTBC attenuated HG/PA-induced INS-1 cell injury through the promotion of SIRT1-mediated suppression of ROS accumulation and apoptosis. This is the first study to comprehensively identify the lncRNA expression profiling of HG/PA-treated INS-1 beta cells and to demonstrate that LEGLTBC functions as a competing endogenous RNA and regulates miR-34a/SIRT1-mediated oxidative stress and apoptosis in INS-1 cells undergoing glucolipotoxicity.

Responsiveness of hypothalamo-pituitary-adrenal axis to leptin is impaired in diet-induced obese rats

Background/objectivesDiet-induced obese (DIO) rats have altered stress (HPA) axis activity compared to diet-resistant (DR) rats when chronically exposed to a high-fat (HF) diet. Since stress axis is tightly regulated by leptin, an adipocyte-secreted hormone that is important for controlling body weight, we hypothesized that leptin action is impaired in DIO rats leading to alterations in HPA axis activity.Subjects/methodsWe intraperitoneally injected selectively bred DIO and DR rats with either saline or recombinant rat leptin. HPA axis activity was assessed by measuring norepinephrine (NE) in the paraventricular nucleus (PVN), corticotropin-releasing hormone (CRH) in the median eminence, and serum corticosterone (CORT). To test if HF exposure duration and the corresponding increase in leptin differentially affects HPA axis activity, we placed animals on a chow or HF diet for 1 or 6 weeks.ResultsLeptin injection significantly increased serum leptin levels in both DIO and DR animals. It also reduced PVN NE in both groups, indicating that noradrenergic neurons in both groups remain responsive to leptin. HF diet duration-dependently increased serum leptin only in DIO animals whereas PVN NE increased in both groups. While DR rats responded to HF diet by increasing CRH and CORT at both time-points, responses in DIO rats varied, suggesting that they have altered HPA axis activity that may be dependent on HF-induced leptin levels and/or signaling. To understand the underlying mechanisms, we measured pSTAT-3, a marker of leptin signaling, in brainstem noradrenergic neurons and found reduced pSTAT-3 in A1 region of HF-fed DIO rats. We also found higher serum free fatty acids (FFAs) and a pro-inflammatory cytokine, IL-1β.ConclusionsCollectively, these findings reveal that DIO rats have inherent neuroendocrine impairment in NE-HPA axis circuitry that worsens with the extent of HF diet exposure, possibly due to brainstem leptin resistance and/or elevated circulating FFAs and IL-1β.

High serum free fatty acids and low leptin levels: Plausible metabolic indicators of negative energy balance in early lactating Murrah buffaloes.

Lactation is a highly demanding event in mammals, including buffaloes. It modulates the partitioning of nutrients, energy utilization, and food intake of the mother to meet her own and infant's energy needs. Failure to satisfy these energy needs leads to Negative Energy Balance (NEB). Currently, the only available indirect NEB indicator is Body Condition Score (BCS). However, direct dependency of the BCS on the peak depletion of body fat causes its inefficient use in a dairy farm. Thus, to establish objective NEB indicators in buffaloes, the serum levels of biochemical (serum β-hydroxybutyrate [BHBA] and free fatty acids [FFAs]), and endocrine (Growth Hormone [GH], insulin-like growth factor1 [IGF1], Insulin, and leptin) parameters were estimated in buffaloes. Our results revealed that serum FFA levels were significantly (p < 0.05) higher in high milk yielders (HMY) than low milk yielders (LMY) and heifers (H) during the 3rd and the 4th weeks of postpartum. The serum FFA levels were also significantly (p < 0.001) higher in the postpartum buffaloes with BCS < 3 in the field conditions. Further, serum leptin levels were significantly (p < 0.05) lower in HMY than LMY during the 3rd week of postpartum. However, the BHBA, GH, IGF1, and insulin levels were not significantly different between lactating buffaloes and H. These observations indicated that the NEB condition is probably restricted to the first month of early lactation in buffaloes. In conclusion, the simultaneous higher FFA and lower leptin levels could act as direct plausible metabolic indicators of NEB in buffaloes.

Associations between hypertension and the peroxisome proliferator-activated receptor-\u03b4 (PPARD) gene rs7770619 C>T polymorphism in a Korean population

BackgroundOxidative stress is associated with the increased risk of hypertension (HTN). This cross-sectional study is aimed to identify the association between the peroxisome proliferator-activated receptor-δ (PPARD) polymorphism and plasma malondialdehyde (MDA), an oxidative stress marker which is related to HTN development, and to determine whether PPARD gene is a candidate gene for HTN.ResultsOne thousand seven hundred ninety-three individuals with normal blood pressure (BP) and HTN were included in this cross-sectional study. The Korean Chip was used to obtain genotype data. Through the analysis, the ten most strongly associated single-nucleotide polymorphisms (SNPs) were nominated for an MDA-related SNP. Among them, the rs7770619 polymorphism was identified in the PPARD gene. The CT genotype of the PPARD rs7770619 C>T polymorphism was associated with a lower risk of HTN before and after adjustments for age, sex, body mass index, smoking, and drinking. Significant associations were observed between plasma MDA and the PPARD rs7770619 C>T polymorphism and between systolic BP and the PPARD rs7770619 SNP in the controls. The CT controls showed significantly lower systolic BP and plasma MDA than the CC controls. Additionally, in both controls and HTN patients, the CT subjects showed significantly lower serum glucose and higher adiponectin levels than the CC subjects. Furthermore, the CT subjects showed significantly higher serum free fatty acid levels than the CC subjects among the HTN patients.ConclusionThis is a new finding that the PPARD rs7770619 C>T SNP is a novel candidate variant for HTN based on the association between PPARD and plasma MDA in a Korean population.

Hepatic Steatosis Markers in Diabetic Rats Trained at the Aerobic/ Anaerobic Transition

Aims: To analyze the effects of exercise performed at the aerobic/anaerobic transition (Lan) on Non-Alcoholic Hepatic Steatosis (NAHS) markers in type 1 diabetic rats. Methods: Adult Wistar rats were separated into four groups: Sedentary Control (SC), Trained Control (TC), Sedentary Diabetic (SD) and Trained Diabetic (TD). The trained groups swam supporting workloads equivalent to the Lan for one hour/day, five days/week, for eight weeks. Body weight, serum albumin concentrations, glucose concentrations, Free Fatty Acid (FFA) concentrations, NAHS markers (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) and total lipid concentrations in the liver were analyzed. Results: The diabetic groups showed higher serum glucose concentrations and more weight loss compared to the controls, although the TD group was less affected than the SD group. Training resulted in a decrease in serum glucose levels in the diabetic rats. The NAHS markers, total lipid concentrations in the liver and serum albumin concentrations did not differ between the groups. However, the diabetic animals had higher serum FFA levels than the controls. Conclusion: Physical training at Lan attenuates weight loss and improves serum glucose homeostasis in diabetic animals. In addition, serum ALT and AST enzymes proved to be adequate markers of lipid levels in the livers in this animal model.

Effect of NAD on PARP-mediated insulin sensitivity in oleic acid treated hepatocytes.

High serum free fatty acids levels are associated with the development of insulin resistance in type 2 diabetes; however, the precise mechanisms underlying this lipid toxicity are unclear. To investigate whether PARP1 activation and NAD depletion are involved in the impairment of insulin sensitivity associated with lipotoxicity, HepG2 cells were cultured with 500 μM oleic acid for 48 h. Oleic acid-treated cells exhibited increased ROS generation, lipid accumulation and PARP1 activation. Treatment with the PARP1 inhibitor PJ34 and transfection with PARP1 small interfering RNA both prevented the oleic acid-induced impairment of the insulin signaling pathway. Furthermore, treatment with PJ34 reversed the oleic acid-induced decrease in intracellular NAD concentration, while exogenous NAD protected cells against oleic acid-induced insulin insensitivity. Combined NAD and PJ34 administration did not enhance the effects obtained by treatment with either NAD or PJ34 alone. Interestingly, when cells were treated with the SIRT1 inhibitor EX527, the protective effects of PJ34 and NAD treatment were diminished. Taken together, these data suggest that NAD depletion by PARP1 activation is essential for the modulation of insulin sensitivity in oleic acid-induced lipotoxicity.

Peripheral insulin resistance in obese girls with hyperandrogenism is related to oxidative phosphorylation and elevated serum free fatty acids.

Hyperandrogenic syndrome (HAS) is associated with insulin resistance (IR) and type 2 diabetes. Muscle IR in type 2 diabetes is linked with defects in mitochondrial oxidative capacity. In vivo muscle mitochondrial function has not been studied in HAS, especially in youth, who are early in the disease process. Our goal was to measure muscle mitochondrial oxidative function and peripheral IR in obese youth with HAS. Obese girls without HAS [n = 22, age 15(13,17) yr, BMI Z-score 2.05 ± 0.37] and with HAS [n = 35, age 15(14,16) yr, BMI Z-score 2.18 ± 0.30] were enrolled. Mitochondrial function was assessed with (31)phosphorus MR spectroscopy before, during, and after near-maximal isometric calf exercise, and peripheral IR was assessed with an 80 mU·m(-2)·min(-1) hyperinsulinemic euglycemic clamp. Girls with HAS had higher androgens [free androgen index 7.9(6.6,15.5) vs. 3.5(3.0,4.0), P < 0.01] and more IR [glucose infusion rate 9.4(7.0, 12,2) vs. 14.5(13.2,15.8) mg·kg lean(-1)·min(-1), P < 0.01]. HAS girls also had increased markers of inflammation including CRP, platelets, and white blood cell count and higher serum free fatty acids during hyperinsulinemia. Mitochondrial oxidative phosphorylation was lower in HAS [0.11(0.06,0.19) vs. 0.18(0.12,0.23) mmol/s, P < 0.05], although other spectroscopy markers of mitochondrial function were similar between groups. In multivariate analysis of the entire cohort, IR related to androgens, oxidative phosphorylation, and free fatty acid concentrations during hyperinsulinemia. These relationships were present in just the HAS cohort as well. Obese girls with HAS have significant peripheral IR, which is related to elevated androgens and free fatty acids and decreased mitochondrial oxidative phosphorylation. These may provide future options as targets for therapeutic intervention.

Early biochemical changes and histological analysis in adipose tissue and liver of rats fed high‐fat diet (HFD) with different fatty acid composition

Early metabolic alterations induced by a high content of fat in diet are poorly understood and less is known about if the type of fat play an important role in lipid metabolism, thus we studied rats fed 7 or 21% fat in diet for 21 d. Fat sources were coconut (CO), safflower (SF) or soybean (SB) oil. Our results showed minor significant differences in the biochemical and hormonal variables among groups during fast. Interestingly, rats fed CO had higher serum insulin in fed state resulting in lower serum glucose in comparison to SF and SB and was attenuated with HFD. On the other hand, rats fed HFD showed higher serum free fatty acids (FFA), glycerol and triglycerides during the fed state, independently of the type of dietary fat. In addition, as excepted, rats fed HFD (21%) had lower serum adiponectin. No significant changes were observed for serum cholesterol, leptin and glucagon. These results indicate that in 3 wks, consumption of a HFD produced biochemical abnormalities of carbohydrate and lipid metabolism. Histological analysis showed that rats fed 21% CO have some hepatic fat deposition and larger adipocytes. Thus, consumption of CO increased postprandial insulin release and a HFD increased lipolysis in fed state. These results also showed that previously to body weight changes, metabolic alterations induced by HFD occurred first in the fed state rather than in fast. Supported by Conacyt.

Association between metabolic abnormalities and HBV related hepatocelluar carcinoma in Chinese: A cross-sectional study

BackgroundPrevious studies suggested that the abnormality of metabolism is a newly identified risk factor in HBV-related hepatocellular carcinoma (HCC). The association between metabolic factors and hepatocellular carcinoma (HCC) has not been clarified up to now. This study was conducted to investigate the prevalence of metabolic abnormalities in HCC and to probe the association between metabolic parameters and liver function as well, so as to evaluate the interactions between metabolism and the development of HBV-related HCC.MethodsTotally 179 cases of HBV-related HCC, who were surgically treated and pathologically confirmed were enrolled. HBV carriers (n = 100) and healthy controls (n = 150) were recruited from routine physical examination during the same period. Body mass index (BMI) was obtained from medical documentation. All the metabolic-related parameters and liver function tests were determined with routine biochemical or immunological analytic methods. Malondialdehyde (MDA) and total antioxidant capacity(TAOC)were detected by chemical analytic methods. A stratified analysis was conducted according to BMI, glycated albumin (GA), free fatty acids (FFA), and the relationships between the metabolic-related parameters and liver functions were analyzed in HCC and control subjects.ResultsHCC group showed significantly high levels of mean BMI, serum glucose, low serum lipids levels than controls (P < 0.05). Acquired by stratified analysis, the higher the BMI, the higher level of insulin and homeostasis model assessment for insulin resistance (HOMA-IR) (P < 0.01) were found in HCC patients. Elevated level of MDA and γ-glutamyltransferase (GGT) were revealed in those with high serum FFA level for the first time. Strong associations between metabolic factors and liver function were shown in HCC (P < 0.05). Higher GA level was strongly associated with increased risk of cancer compared to healthy controls (OR = 9.87, 95% confidence interval: 1.86~52.29). Serum triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels were negative contributory factors for HCC (OR = 0.05, 95% confidence interval: 0.01~0.27 and OR = 0.32, 95% confidence interval, 0.11~0.95: respectively).ConclusionsMetabolic abnormalities are closely associated with the occurrence and development of HBV-related HCC. Oxidative stress and/or lipid peroxidation might be involved in the pathogenesis and acceleration of liver function impairments in HCC.

Medium-chain triglycerides impair lipid metabolism and induce hepatic steatosis in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient mice

A medium-chain-triglyceride (MCT)-based diet is mainstay of treatment in very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), a long-chain fatty acid β-oxidation defect. Beneficial effects have been reported with an MCT-bolus prior to exercise. Little is known about the impact of a long-term MCT diet on hepatic lipid metabolism. Here we investigate the effects of MCT-supplementation on liver and blood lipids in the murine model of VLCADD. Wild-type (WT) and VLCAD-knock-out (KO) mice were fed (1) a long-chain triglyceride (LCT)-diet over 5 weeks, (2) an MCT diet over 5 weeks and (3) an LCT diet plus MCT-bolus. Blood and liver lipid content were determined. Expression of genes regulating lipogenesis was analyzed by RT-PCR. Under the LCT diet, VLCAD-KO mice accumulated significantly higher blood cholesterol concentrations compared to WT mice. The MCT-diet induced severe hepatic steatosis, significantly higher serum free fatty acids and impaired hepatic lipid mobilization in VLCAD-KO mice. Expression at mRNA level of hepatic lipogenic genes was up-regulated. The long-term MCT diet stimulates lipogenesis and impairs hepatic lipid metabolism in VLCAD-KO mice. These results suggest a critical reconsideration of a long-term MCT-modified diet in human VLCADD. In contrast, MCT in situations of increased energy demand appears to be a safer treatment alternative.

Effect of raisin consumption on oxidative stress and inflammation in obesity

Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high-fat meal in overweight individuals. Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low-flavonoid diet. The oxidative [urinary 8-iso-prostaglandin-F(2alpha) (8-epi PGF(2alpha)) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C-reactive protein and interleukin-6), endothelial (serum soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1, sVCAM-1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high-fat (53%) meals was tested pre- and postintervention. Urinary 8-epi PGF(2alpha) decreased (-22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein-free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM-1 and glucose compared with females. Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress.

Therapeutic Challenge to Adiposity of the Heart

See related article, pages 1208–1217 The recent increase in the prevalence of obesity is one possible explanation for the adverse trends in cardiovascular morbidity and mortality. Hospitalizations for congestive heart failure have increased, and the decline in death because of coronary heart disease has leveled off. In parallel with these aspects, there is emerging evidence that inherited and acquired cardiomyopathies are associated with marked intracellular lipid accumulation in the heart.1–5 Three types of mismatches between uptake and utilization of long chain fatty acid (LCFA) lead to abnormally high intracellular LCFA concentrations in the heart, resulting in lipotoxic cardiomyopathy. First, inborn errors in myocardial β-oxidation are associated with heart failure, arrhythmias, sudden death, and pathologic lipid accumulation with a 3-fold increase in phospholipids and 100-fold increase in triglycerides in the myocardium.1 Second, myocardial metabolism switches from utilization of LCFA to utilization of glucose during the development of cardiac hypertrophy and in the ischemic and failing heart. Although this metabolic switch initially serves an adaptive function, accumulation of intracellular LCFA in these acquired conditions contributes to contractile dysfunction and the generation of cardiac arrhythmias.2 Third, several-fold increased cardiac myocyte triglyceride stores are observed in animal models of obesity and diabetes, in which high serum free fatty acid levels promote LCFA uptake in excess of tissue capacity for utilization.3,4 This lipid accumulation contributes to cardiac myocyte apoptosis by nonoxidative metabolic pathways, such as ceramide synthesis, and to congestive heart failure (Figure). Even in humans, myocardial lipid content has been recently reported to increase with the degree of adiposity and contribute to the adverse structural and functional cardiac adaptations, suggesting that myocardial lipid content is a biomarker and putative therapeutic target for cardiac disease in obese patients.5 Indeed, one trial of the medium-chain triglyceride-enriched diet rescued the baseline …

Maternal diet composition alters serum steroid and free fatty acid concentrations and vaginal pH in mice

We examined the effects of three maternal diets (very high fat (VHF), low fat (LF), and control (Purina 5015)) on serum steroids, free fatty acids (FFA), and vaginal pH in National Institutes of Health Swiss mice. Females were fed (VHF, n = 33; LF, n = 33; 5015, n = 48) from 4 to 16 weeks of age. Following breeding, female serum was collected at 0.5 (pre-implantation, early diestrus) or 8.5 (post-implantation, mid-diestrus) days post-coitus (dpc). The serum concentrations of 17beta-estradiol, testosterone, progesterone, and FFA were analyzed at both collection points, and vaginal pH at 0.5 dpc. Striking differences in steroids and FFA were observed at 0.5 dpc among the groups. Estradiol was higher in the VHF (14.1 +/- 3.0 pg/ml), compared with LF mice (5.2 +/- 2.3 pg/ml; P< or = 0.05). In contrast, 0.5 dpc testosterone was lower in the VHF (10.5 +/- 3.0 pg/ml) versus the LF group (32.7 +/- 8.4 pg/ml; P< or = 0.05). At 8.5 dpc, progesterone was higher in the VHF (89.6 +/- 6.7 ng/ml) versus the 5015 group (60.1 +/- 4.9 ng/ml; P< or = 0.05). VHF mice had higher FFA concentrations at 0.5 dpc (1.0 +/- 0.2 mmol/l) than LF and control mice (0.5 +/- 0.1 and 0.6 +/- 0.1 mmol/l respectively; P< or = 0.05). At 8.5 dpc, VHF females had higher serum FFA (0.8 +/- 0.1 mmol/l) than LF and control females (0.4 +/- 0.1 and 0.6 +/- 0.1 mmol/l; P< or = 0.05). Mean vaginal pH of VHF females (6.41 +/- 0.09) was lower than 5015 females (6.76 +/- 0.10; P< or = 0.05). These diet-induced alterations in serum steroid and FFA concentrations might affect several reproductive processes, including preferential fertilization by one class of sperm over the other and sex bias in pre- and post-implantational embryonic development.

Reduced adiposity in bitter melon (Momordica charantia) fed rats is associated with lower tissue triglyceride and higher plasma catecholamines

Slower weight gain and less visceral fat had been observed when rats fed a high-fat diet were supplemented with freeze-dried bitter melon (BM) juice; the metabolic consequences and possible mechanism(s) were further explored in the present study. In a 4-week experiment, rats were fed a low-fat (70 g/kg) or a high-fat (300 g/kg) diet with or without BM (7.5 g/kg or 0.75%). BM-supplemented rats had lower energy efficiency, visceral fat mass, plasma glucose and hepatic triacylglycerol, but higher serum free fatty acids and plasma catecholamines. In the second experiment, 7-week BM supplementation in high-fat diet rats led to a lowering of hepatic triacylglycerol (P<0.05) and steatosis score (P<0.05) similar to those in rats fed a low-fat diet. BM supplementation did not affect serum and hepatic cholesterol. However, plasma epinephrine and serum free fatty acid concentrations were increased (P<0.05). In the third experiment, BM(7.5 and 15 g/kg) and 1.5 % BM lowered triacylglycerol concentration in red gastrocnemius and tibialis anterior (P<0.05) muscle, but a dose-response effect was not observed. These data suggest that chronic BM feeding leads to a general decrease in tissue fat accumulation and that such an effect is mediated in part by enhanced sympathetic activity and lipolysis. BM or its bioactive ingredient(s) could be used as a dietary adjunct in the control of body weight and blood glucose.

Effects of different nutritional levels prepartum on the subsequent performance of dairy cows

Different nutritional levels introduced three weeks before calving and gradually reaching the maximum supply level of 110, 170, 200 or >200 (ad lib) MJ ME/day at calving were studied in two experiments comprising altogether 63 multiparous cows. In Experiment 1, the difference at calving (110 vs. 200 MJ) was gradually eliminated within 4 weeks post partum, while in Experiment 2 treatment differences (ad libitum vs. restricted) were practiced throughout the experiment. The feeds (concentrate, grass hay and grass silage) were fed separately in Experiment 1 and as a total mixed ration in Experiment 2. The experimental period lasted from 4 weeks before calving to 12 or 14 weeks afterwards. The average daily intake of metabolizable energy in cows fed ad libitum was 180 MJ prepartum and 307 MJ in early lactation. A marked decrease in feed intake occurred around calving time, beginning 3–5 days prepartum, among all cows fed a medium or highly nutritional diet at calving. A low nutritional level at calving resulted in a significantly smaller milk yield in the first month postpartum and low serum insulin and high serum free fatty acids concentrations around parturition. Ad libitum feeding did not result in higher milk yield but gave a greater milk protein content and yield and also impaired feed efficiency. Health, fertility, and plasma glucose concentrations did not differ between treatments.

Suppressed expression of the urea cycle enzyme genes in the liver of carnitine-deficient juvenile visceral steatosis (JVS) mice in infancy and during starvation in adulthood.

Systemic carnitine-deficient juvenile visceral steatosis (JVS) mice exhibit decreased expression of some liver-selective genes including those for the urea cycle enzymes during the infantile period. At 25 days, carbamoylphosphate synthetase (CPS) mRNA level was remarkably low in the liver of JVS mice, and the HNF-4 and C/EBP-alpha mRNA contents were also reduced. HNF-3 alpha and C/EBP-beta mRNAs were slightly higher in the liver of JVS mice, and HNF-1 mRNA remained normal. These results, together with the developmental changes of these transcription factor mRNA levels, suggest that HNF-4 and C/EBP-alpha are involved in the suppression of CPS expression. If JVS mice survived the crisis at 4-5 weeks, their body weight caught up with that of control mice around 7 weeks. The steady-state levels of CPS and argininosuccinate synthetase (ASS) mRNAs in the liver of JVS mice were normalized by no later than 8 weeks. Starvation for 48 h caused an increase of about twofold in CPS and ASS mRNA levels in the liver of control mice, while the same treatment failed to increase their levels in the liver of JVS mice. The starvation similarly caused increases in HNF-4 and C/EBP-beta mRNA levels in the liver of both control and JVS mice, but the increases were significantly less in JVS mice than in control mice. Thus, the lack of induction of CPS and ASS mRNAs during development and under starvation in JVS mice correlated with the lower induction of HNF-4 and C/EBP-alpha mRNAs, and of HNF-4 and C/ EBP-beta mRNAs, respectively. Furthermore, all these changes seemed to correlate with the presence of fatty liver and the high serum free fatty acid levels, suggesting that disturbance of fatty acid metabolism affects nitrogen metabolism at least in part via altered gene expression of transcription factors such as HNF-4, C/EBP-alpha, and C/EBP-beta.

Fasting Serum Free Fatty Acids and Triglycerides are Increased Before 20 Weeks of Gestation in Women who Later Develop Preeclampsia

Objective: The null hypothesis of this study was that there was no difference in fasting serum concentrations of free fatty acids (FFA) and triglycerides (TG) before 20 weeks of gestation in women who later develop preeclampsia, compared to women with uneventful pregnancies.Methods: Healthy primigravida, n = 510, provided fasting blood samples at 16-18 weeks of gestation. Nineteen of these later developed preeclampsia. Nineteen matched controls were selected from the remaining 491 individuals. Blood samples were also obtained from 16 patients with manifest preeclampsia and from 16 control women with uncomplicated pregnancies. Concentrations of FFA and TG, and the lipolytic activity in maternal serum were measured.Results: In patients with manifest preeclampsia, serum levels of FFA and TG, and lipolytic activity were significantly increased compared to women with normal pregnancies. The group of 19 women who later developed preeclampsia had higher serum FFA and TG concentrations at 16-18 weeks of gestation compared to a matched control group: FFA 0.50 0.15 vs. 0.34 0.11 mmol/L (P < 0.001) and TG 1.3 0.5 vs. 0.9 0.3 mmol/L (P = 0.003).Conclusion: We provide for the first time evidence that fasting serum free fatty acids and triglycerides are increased before 20 weeks of gestation in women who later develop preeclampsia.