Retroperitoneal Fat Pad Weight Research Articles

Pharmacological Antagonism of the Kisspeptin-Neurokinin System Improved Adverse Metabolic Traits in a PCOS Mouse Model

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine condition affecting up to 20% of reproductively aged women worldwide. Owing to an ambiguous etiology and complicated pathophysiology, current PCOS treatments remain purely symptomatic. Aberrations in androgen receptor driven neuroendocrine pathways are reportedly involved in the pathogenesis of PCOS. A clinical trial, focusing on the androgen regulated kisspeptin-neurokinin B-dynorphin system, treated women with PCOS with a neurokinin B receptor (neurokinin 3 receptor, NK3R) antagonist and reported improvements in LH secretion, LH pulses and testosterone levels. Aim: To investigate if pharmacological antagonism of NK3R can ameliorate PCOS traits in a mouse model. Method: Reproductive and metabolic features of PCOS were evaluated in control and dihydrotestosterone (DHT)-induced PCOS mice, treated +/-NK3R antagonist (MLE4901) for 28 days at a dose of 25mg/kg/day. Results: PCOS-like mice were acyclic and exhibited ovulatory dysfunction, which were not rescued by NK3R antagonist treatment. Compared to control mice, the PCOS-like mice displayed a significant increase in total body weight and inguinal, parametrial, mesenteric, retroperitoneal, and brown fat pad weights (all P[Formula: see text]0.01). NK3R antagonism partially reversed the total body weight and fat pad weight gains (all P[Formula: see text]0.01) in all white fat depots of PCOS-like mice. PCOS-like mice also displayed adipocyte hypertrophy and increased leptin levels compared to control mice (both P[Formula: see text]0.01), which were improved with NK3R antagonism treatment (P[Formula: see text]0.01 and P[Formula: see text]0.05, respectively). Moreover, DHT exposure significantly reduced the respiratory exchange ratio (RER) (P[Formula: see text]0.01), whereas NK3R antagonism significantly increased RER compared to control mice (P[Formula: see text]0.01), suggesting a metabolic shift in the PCOS-like mice treated with the NKR3 antagonist. Conclusion: These findings show that pharmacological antagonism of the kisspeptin-neurokinin system may be a beneficial treatment for adverse metabolic features of PCOS. This study also reveals important new insights into neuroendocrine androgen actions in the pathogenesis of PCOS.

Diabetogenic and Obesogenic Effects of Cadmium in Db/Db Mice and Rats at a Clinically Relevant Level of Exposure.

Studies show an association between cadmium (Cd) exposure and prediabetes or type II diabetes mellitus. We have previously reported that Cd causes decreased levels of serum leptin in rats following 12 weeks of daily Cd dosing (0.6 mg/kg/b.w./day). Since leptin plays an important role in metabolism, we examined the effects of Cd on rats and db/db mice, which are deficient in leptin receptor activity. We gave rats and mice daily subcutaneous injections of saline (control) or CdCl2 at a dose of 0.6 mg/kg of Cd for 2 weeks, followed by 2 weeks of no dosing. At the end of the 4-week study, exposure to Cd resulted in a more rapid increase in blood glucose levels following an oral glucose tolerance test in db/db vs. lean mice. During the two weeks of no Cd dosing, individual rat bodyweight gain was greater (p ≤ 0.05) in Cd-treated animals. At this time point, the combined epididymal and retroperitoneal fat pad weight was significantly greater (p ≤ 0.05) in the Cd-treated lean mice compared to saline-treated controls. Although this pilot study had relatively low N values (4 per treatment group for mice and 6 for rats) the results show that clinically relevant levels of Cd exposure resulted in diabetogenic as well as obesogenic effects.

Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation.

Metabolic syndrome (MetS) is an important cause of worldwide morbidity and mortality. Its complex pathogenesis includes, on the one hand, sedentary lifestyle and high caloric intake, and, on the other hand, there is a clear genetic predisposition. PD (Polydactylous rat) is an animal model of hypertriglyceridemia, insulin resistance, and obesity. To unravel the genetic and pathophysiologic background of this phenotype, we compared morphometric and metabolic parameters as well as liver transcriptomes among PD, spontaneously hypertensive rat, and Brown Norway (BN) strains fed a high-fat diet (HFD). After 4 weeks of HFD, PD rats displayed marked hypertriglyceridemia but without the expected hepatic steatosis. Moreover, the PD strain showed significant weight gain, including increased weight of retroperitoneal and epididymal fat pads, and impaired glucose tolerance. In the liver transcriptome, we found 5480 differentially expressed genes, which were enriched for pathways involved in fatty acid beta and omega oxidation, glucocorticoid metabolism, oxidative stress, complement activation, triacylglycerol and lipid droplets synthesis, focal adhesion, prostaglandin synthesis, interferon signaling, and tricarboxylic acid cycle pathways. Interestingly, the PD strain, contrary to SHR and BN rats, did not express the Acsm3 (acyl-CoA synthetase medium-chain family member 3) gene in the liver. Together, these results suggest disturbances in fatty acid utilization as a molecular mechanism predisposing PD rats to hypertriglyceridemia and fat accumulation.

Red Yeast Rice Mitigates High-Fat Diet Induced-Obesity Related Vascular Dysfunction in Wistar Albino Rats

The red yeast rice methanolic extract (RYR) was suggested to have promising therapeutic effects against vascular endothelial dysfunction. In the present study, the protective effects of RYR at 200 and 400 mg/kg/day were investigated in a specific animal model that exhibits a high-fat diet (HFD)-induced dyslipidemia and vascular endothelium dysfunction. Vascular endothelial reactivity experiments were evaluated using aorta obtained from adult rats in an ex-vivo organ bath setup. Three consecutive weeks of RYR treatment exhibited a significant reduction in body weight (BW), liver weight (LW), and retroperitoneal fat pad weight (RFPW)/BW ratios as compared to HFD only treated rats where a significant body weight gain was observed. RYR treatment also significantly decreased the average daily food intake, waist, lee index, and body mass index compared to rats treated with HFD only. RYR treatment significantly reduced total cholesterol, triglyceride, low-density lipoprotein, and very-low-density lipoprotein levels compared to the HFD group. HFD-induced endothelium dysfunction in the aorta of animals was reversed by RYR treatment, comparable to the HFD group. RYR treatment, specifically at 400 mg/kg/day dose, revealed a significant protective effect on vascular endothelium and an improvement in the lipid panel, hence justifying therapeutic involvement of RYR in dyslipidemia and endothelial dysfunctions.

Risperidone Exacerbates Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Renal Impairment in Obese Mice.

Risperidone, a second-generation antipsychotic drug used for schizophrenia treatment with less-severe side effects, has recently been applied in major depressive disorder treatment. The mechanism underlying risperidone-associated metabolic disturbances and liver and renal adverse effects warrants further exploration. This research explores how risperidone influences weight, glucose homeostasis, fatty liver scores, liver damage, and renal impairment in high-fat diet (HFD)-administered C57BL6/J mice. Compared with HFD control mice, risperidone-treated obese mice exhibited increases in body, liver, kidney, and retroperitoneal and epididymal fat pad weights, daily food efficiency, serum triglyceride, blood urea nitrogen, creatinine, hepatic triglyceride, and aspartate aminotransferase, and alanine aminotransferase levels, and hepatic fatty acid regulation marker expression. They also exhibited increased insulin resistance and glucose intolerance but decreased serum insulin levels, Akt phosphorylation, and glucose transporter 4 expression. Moreover, their fatty liver score and liver damage demonstrated considerable increases, corresponding to increases in sterol regulatory element-binding protein 1 mRNA, fatty acid-binding protein 4 mRNA, and patatin-like phospholipid domain containing protein 3 expression. Finally, these mice demonstrated renal impairment, associated with decreases in glutathione peroxidase, superoxide dismutase, and catalase levels. In conclusion, long-term administration of risperidone may exacerbate diabetes syndrome, nonalcoholic fatty liver disease, and kidney injury.

Genome-Wide Association Study in 3,173 Outbred Rats Identifies Multiple Loci for Body Weight, Adiposity, and Fasting Glucose.

Obesity is influenced by genetic and environmental factors. Despite the success of human genome-wide association studies, the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify the genetic loci underlying obesity and related morphometric and metabolic traits. This study measured obesity-relevant traits, including body weight, body length, BMI, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat genome-wide association study to date. Genetic loci were identified using a linear mixed model to account for the complex family relationships of the HS and using covariates to account for differences among the three phenotyping centers. This study identified 32 independent loci, several of which contained only a single gene (e.g., Epha5, Nrg1, Klhl14) or obvious candidate genes (e.g., Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity-related traits, and there was extensive pleiotropy at individual loci. This study demonstrates the utility of HS rats for investigating the genetics of obesity-related traits across institutions and identify several candidate genes for future functional testing.

The high-fructose intake of dams during pregnancy and lactation exerts sex-specific effects on adult rat offspring metabolism.

Experimental studies have demonstrated the effects of maternal fructose consumption during pregnancy and lactation on metabolic alterations in their offspring, especially male offspring. However, few studies have focused on female offspring after providing fructose in food to dam rats. Here, we studied whether offspring of both sexes were differentially affected by a maternal high-fructose diet (HFD). For this purpose, Sprague-Dawley rats were fed during pregnancy and lactation with a standard diet (SD) or a HFD (50% w/w). After weaning, offspring were fed an SD; 3 days later, dams were sacrificed, and their offspring were sacrificed on postnatal day 90. Body weight (BW), food and water intake (only for dams), and various biomarkers of metabolic syndrome were measured. When compared to the SD-fed dams, HFD-fed dams had a reduction in BW and food and water intake. Conversely, adiposity, liver weight, liver lipids, and plasma levels of glucose, insulin, cholesterol, triglycerides, and uric acid were increased in HFD-fed dams. Moreover, the BW, food consumption, weight of retroperitoneal fat pads, and liver lipids increased in female and male offspring of HFD-fed dams. Interestingly, the pups of HFD-fed mothers showed increased levels of leptin and insulin resistance and decreased levels of adiponectin which were more pronounced in male offspring than in female offspring. In contrast, a higher increase in BW was shown earlier in female offspring. Thus, high-fructose consumption by dams during pregnancy and lactation led to sex-specific developmental programming of the metabolic syndrome phenotype in adult offspring.

Potential of Aerobic Physical Training to Minimize the Effects of Leptin Deficiency in Female Mice

Aerobic physical training (APT) is an important strategy for prevention and treatment of comorbidities such as type 2 diabetes and obesity. Leptin and adiponectin play an important role in energy metabolism, whose imbalance is strongly related to obesity and insulin resistance (IR). Although women have higher levels of leptin and adiponectin compared to men, in conditions such as obesity and/or type 2 diabetes these levels decrease, abolishing the protective effects of these adipokines in females. This study investigated the effects of APT on the metabolic parameters in leptin‐deficient female mice. For this, 8‐week‐old wild C57BL/J6 (C57) or leptin‐deficient ob/ob (Lepob) female mice were separated into the groups sedentary (S) (C57S, n = 6 and LepobS, n = 5) and trained (T) (LepobT, n = 8). The APT was performed during 1 h/day at 60% of maximal speed achieved in the maximal physical exertion test, 5 times/week for eight weeks. The procedures were approved by the Ethics Committee of the School of Arts, Sciences and Humanities of University of Sao Paulo (#001/2017). LepobS and LepobT groups increased body weight, the weight of retroperitoneal (WAT‐RP) and subcutaneous (WAT‐SC) fat pads compared to C57S. Adipocyte area and diameter of WAT‐RP and WAT‐SC were higher in both LepobS and LepobT compared to C57S, however the APT decreased the WAT‐SC adipocyte area and diameter in LepobT group compared to LepobS. LepobS and LepobT groups showed lower weight of pancreas, gastrocnemius and plantar muscles compared to C57S, however APT prevented the mass reduction of gastrocnemius and plantar muscles in LepobT. Food intake was higher in LepobS compared to C57S, which was counteracted by APT in the LepobT group. The LepobS had fasting hyperglycemia (131 ± 1.02 mg/dL) and glucose intolerance (AUC: 31522 ± 1148 mg/dL/120min) compared to C57S (92 ± 2.51 mg/dL and AUC: 20339 ± 1857 mg/dL/120min). Despite of LepobT group had shown glucose intolerance (AUC: 30085 ± 547 mg/dL/120min), the APT decreased the fasting glycemia (114 ± 6.11 mg/dL) compared to LepobS group. Adiponectin level did not change among groups, as well as the relative area of islets in the pancreatic tissue. During the maximal physical exertion test, LepobT showed higher maximal speed, time to exhaustion and speed on the VO2máx compared to LepobS group. In conclusion, APT prevented the loss of gastrocnemius and plantar muscles mass, reduced WAT‐SC adipocyte hypertrophy and food intake, improved fasting glycemia and aerobic capacity in leptin deficient female mice.Support or Funding InformationFAPESP (#2018/22361‐9), CAPES, CNPq

Are Bisphosphonates Associated with Adverse Metabolic and Cognitive Effects? A Study in Intact Rats and Rats Fed High-Fat High-Fructose Diet.

Osteocalcin, known as a bone gla protein, is considered a regulator of energy metabolism and behavior in its undercarboxylated form (ucOC). Antiresorptive drugs, such as alendronate, reduce serum level of ucOC. The purpose of the current study was to verify if alendronate might impact on energy metabolism and animal behavior by reducing ucOC level and to find out if the presence of metabolic alterations would further worsen these potential adverse effects. Four groups of male Wistar rats (12 per group) were used: a control group, a group receiving high-fat high-fructose diet (HFHF), a group treated with alendronate, and a group receiving alendronate and HFHF. Alendronate was administered subcutaneously in a dose of 50 mcg/kg thrice weekly. Study duration was 15weeks. Animals were tested for locomotion, anxiety and spatial memory. Glucose and insulin tolerance tests evaluated the glucose metabolism. Visceral obesity was assessed by the weight of right retroperitoneal fat pads. Concentration of ucOC was measured in the serum. Alendronate reduced serum ucOC concentration, increased fasting blood glucose level, and worsened insulin sensitivity. It did not increase visceral adiposity. Fat index was negatively correlated with ucOC in all animals and in the alendronate-treated rats. Alendronate worsened spatial memory of the animals and ucOC levels correlated positively with their cognitive performance.

Gochujang prepared using rice and wheat koji partially alleviates high-fat diet-induced obesity in rats.

The aim of this study was to compare whether gochujang products prepared using giant embryo rice koji (rice gochujang, RG) and wheat koji (wheat gochujang, WG) have anti‐obesity effects on rats fed a high‐fat diet (HFD), who served as a model for obesity. The nutritional composition of RG and WG including proximate constituents, amino acid and fatty acid compositions were investigated. Consequently, the secondary fermented metabolites were analyzed in RG and WG by ultrahigh‐performance liquid chromatography and mass spectrometry. Rats were fed a HFD containing 10% RG powder (HFD‐RG) or 10% WG powder (HFD‐WG) for 8 weeks. Body weight gain, weights of liver, epididymal, retroperitoneal, perirenal, and total white fat pads, and levels of serum triglyceride (TG), total cholesterol, low‐density lipoprotein cholesterol, and leptin were lower in all gochujang groups than in the HFD group. Furthermore, RG and WG treatment decreased the hepatic TG content and lipid accumulation and significantly reduced the size of epididymal adipocytes. These effects are probably mediated through inhibition of hepatic fatty acid synthase, acetyl CoA carboxylase, malic enzyme, and adipose tissue lipoprotein lipase activities. The anti‐obesity effect was slightly greater in the HFD‐RG group than in the HFD‐WG group. This effect may be attributed to secondary metabolites, such as capsaicin, genistein, daidzein, soyasaponin, and lysophosphatidylcholines, contained in gochujang prepared using giant embryo rice or wheat koji.

Effect of oat and soybean rich in distinct non-starch polysaccharides on fermentation, appetite regulation and fat accumulation in rat

Consumption of non-starch polysaccharides (NSP) is associated with reduced risk of obesity. This study aimed to compare the effects of cereals (oats) and legumes (soybean), rich in different classes of NSP, on appetite regulation and fat accumulation in rats. Soy pectin fermented more efficient than cereal arabinoxylan in rats. Soy pectin and oat β-glucan were utilized mainly in the caecum of rats. Only small amount of maltodextrin, cello-oligosaccharides and xylo-oligosaccharides were detected in the digesta. Caecal fermentation of soy pectin produced significantly higher concentration of short chain fatty acids (SCFAs) compared to the control. Retroperitoneal (RP) fat-pad weight was significantly lower for rats fed with soybean meal enriched diet than for controls. An inverse correlation between rat RP fat-pad weight and concentration (and proportion) of butyrate was observed. Consumption of soy pectin and oat β-glucan enriched foods to produce targeted SCFAs in vivo could be a potential strategy to lower fat mass accumulation and a potential tool to manage obesity.

Kidney osteoclast factors and matrix metalloproteinase expression in a mice model of diet-induced obesity and diabetes

The role of RANKL/RANK/OPG system on bone remodeling is well known, and there is evidence that it is also important to cardiovascular and kidney pathology, although the underlying mechanisms are not elucidated so far. Thus, we investigated in a mice model of diet-induced obesity and diabetes if renal histopathological changes are associated with the expression of RANKL/RANK/OPG system and matrix metalloproteinases (MMPs). Three months old C57BL/6 mice were fed with control (C) AIN93 M diet or high-fat high sucrose (HFHS) diets for 21 weeks (CEUA/UFF #647/15). The two groups presented weight gain, but it was higher in the HFHS group compared to the C group (+35%, P = 0.0001). The HFHS group also had increased epididymal, inguinal and retroperitoneal fat pad weight (+121%, P = 0.0006; +287%, P = 0.0007 and; +286%, P < 0.0001, respectively), and hyperglycemia (+43%, P = 0.02). The kidney of some HFHS fed mice displayed mononuclear inflammatory cell infiltrate (40%), perivascular fibrosis (20%), and focal tubule mineralization (20%). Glomeruli hypertrophy was not detected. Unexpectedly, OPG, RANK, MMP-2, and MMP-9 expression was not altered in HFHS groups (Western blot analysis). In conclusion, the expression of RANKL/RANK/OPG system proteins and MMPs was not influenced by diet-induced obesity and diabetes in the kidney of male C57BL/6 mice, although some adverse histopathological remodeling is noticed in the renal tissue.

Telmisartan is effective to ameliorate metabolic syndrome in rat model - a preclinical report.

BackgroundMetabolic syndrome (MS) is known to be associated with hypertension, insulin resistance, and dyslipidemia, and it raises the risk for cardiovascular diseases and diabetes mellitus. Telmisartan is used in clinic as an angiotensin II receptor blocker and it is also identified as activating peroxisome proliferator-activated receptors δ (PPARδ). Activation of PPARδ produced beneficial effects on fatty acid metabolism and glucose metabolism. This study aims to investigate the effects of telmisartan on the modulation of MS in rats fed a high-fat/high-sodium diet.MethodsRats were fed with a high-fat/high-sodium diet and received injections of streptozotocin at low dose to induce MS. Then, rats with MS were treated with telmisartan. The weight, glucose tolerance, and insulin sensitivity were measured. The lipid profiles were also obtained. The weights of retroperitoneal and epididymal fat pads were determined. The role of PPARδ in telmisartan treatment was identified in rats pretreated with the specific antagonist GSK0660.ResultsThe results showed that telmisartan, but not losartan, significantly reduced plasma glucose and plasma insulin, and improved insulin resistance in rats with MS. Telmisartan also decreased blood pressure and lipids more significantly than losartan. Moreover, GSK0660 effectively reversed the effects of telmisartan in the MS rats. In the MS group, telmisartan activated PPARδ to enhance the levels of phosphorylated GLUT4 in muscle or the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver, which was also abolished by GSK0660. Telmisartan is useful to ameliorate hypertension and insulin resistance in rats with MS. Telmisartan improves the insulin resistance through increased expression of GLUT4 and down-regulation of PEPCK via PPARδ-dependent mechanisms.ConclusionTelmisartan has been proven to ameliorate MS, particularly in the prediabetes state. Therefore, telmisartan is suitable to develop for the management of MS in clinics.

Methylnaltrexone potentiates body weight and fat reduction with leptin

Leptin increases energy expenditure by enhancing systemic and brown adipose metabolism. In a neonatal rat model, retroperitoneal fat pad weight decreased significantly in leptin-treated animals, which reduced body weight. As opioids increase feeding, opioid antagonists may decrease food intake and body weight. However, interactions between leptin and the activity of peripheral opioids on body weight and fat accumulation have not been investigated. In this study, the authors evaluated the effects of naloxone (a nonselective opioid antagonist) and methylnaltrexone (a peripherally acting opioid antagonist) on the action of leptin in neonatal rats. Compared with control, the weight gain of pups given a single daily intraperitoneal injection of leptin 0.5 mg/kg, leptin 0.5 mg/kg plus naloxone 0.3 mg/kg, or leptin 0.5 mg/kg plus methylnaltrexone 3.0 mg/kg for 8 consecutive days was significantly reduced (all p < 0.01). Naloxone or methylnaltrexone significantly potentiated leptin's effect on body weight (p < 0.05 or p < 0.01, respectively). After coadministration of leptin plus naloxone or leptin plus methylnaltrexone, weight reduction in the right retroperitoneal fat pads was also significant compared with the reduction after leptin alone (p < 0.05 or p < 0.01, respectively). The data suggest the existence of a peripheral opioid-related mechanism in leptin-active modulation of body weight.

A high salt diet inhibits obesity and delays puberty in the female rat.

Background/ObjectivesProcessed foods are considered major contributors to the worldwide obesity epidemic. In addition to high sugar and fat contents, processed foods contain large amounts of salt. Due to correlations with rising adiposity, salt has recently been proposed to be obesogenic. This study investigated three hypotheses: i) high salt contributes to weight gain and adiposity in juvenile female rats, ii) puberty onset would be altered because salt is known to affect neuronal systems involved in activating the reproductive system, and iii) enhanced adiposity will act synergistically with salt to drive early puberty onset.DesignFemale weanling rats (post-natal day 21, n=105) were fed a low fat/low salt diet, low fat/high salt diet, high fat/low salt diet, or a high salt/high fat diet for 24 days. Metabolic measures, including weight gain, food intake, fecal output, activity, and temperature were recorded in subsets of animals.ResultsBody weight, retroperitoneal and perirenal fat pad weight, and adipocyte size were all lower in animals fed high fat/high salt compared to animals fed high fat alone. Leptin levels were reduced in high fat/high salt fed animals compared to high fat/low salt fed animals. Daily calorie intake was higher initially but declined with adjusted food intake and was not different among groups after 5 days. Osmolality and corticosterone were not different among groups. Fecal analysis showed excess fat excretion and a decreased digestive efficiency in animals fed high fat/low salt but not in animals fed high fat/high salt. Although respiratory exchange ratio was reduced by high dietary fat or salt, aerobic resting metabolic rate was not affected by diet. High salt delayed puberty onset, regardless of dietary fat content.ConclusionsSalt delays puberty and prevents the obesogenic effect of a high fat diet. The reduced weight gain evident in high salt fed animals is not due to differences in food intake or digestive efficiency.

Restricting feeding to the active phase in middle-aged mice attenuates adverse metabolic effects of a high-fat diet

Time-restricted feeding ameliorates the deleterious effects of a high-fat diet on body weight and metabolism in young adult mice. Because obesity is highly prevalent in the middle-aged population, this study tested the hypothesis that time-restricted feeding alleviates the adverse effects of a high-fat diet in male middle-aged (12months) mice. C57BL6/J mice were fed one of three diets for 21–25weeks: 1) high-fat diet (60% total calories from fat) ad-libitum (HFD-AL), 2) HFD, time-restricted feeding (HFD-TRF), and 3) low-fat diet (10% total calories from fat) ad-libitum (LFD-AL) (n=15 each). HFD-TRF mice only had food access for 8h/day during their active period. HFD-TRF mice gained significantly less weight than HFD-AL mice (~20% vs 55% of initial weight, respectively). Caloric intake differed between these groups only during the first 8weeks and accounted for most but not all of their body weight difference during this time. TRF of a HFD lowered glucose tolerance in terms of incremental area under the curve (iAUC) (p<0.02) to that of LFD-AL mice. TRF of a HFD lowered liver weight (p<0.0001), but not retroperitoneal or epididymal fat pad weight, to that of LFD-AL mice. Neither HFD-AL nor HFD-TRF had any effect on performance in the novel object recognition or object location memory tests. Circulating corticosterone levels either before or after restraint stress were not affected by diet. In conclusion, TRF without caloric restriction is an effective strategy in middle-aged mice for alleviating the negative effects of a HFD on body weight, liver weight, and glucose tolerance.

Short-term dietary magnesium restriction lowers spleen iron concentrations in growing rats fed a high-fat diet

Lipotoxicity and dietary inadequacies have been associated with dysregulation of Fe homeostasis in obesity. In this study, we tested the hypothesis that dietary Mg restriction in rats fed a high-fat diet affects Fe concentrations in liver and spleen, tissues related with Fe storage and recycling, respectively. Weanling male Wistar rats (n = 48) were fed either control (ad libitum or pair-fed) or high-fat (Mg-adequate or Mg-restricted; 500 and 150 mg Mg/kg, respectively) diets for 4 weeks. Epididymal and retroperitoneal fat pad weights were used to determine the adiposity index. Serum (colorimetry) and tissue Fe (atomic absorption spectrophotometry) were analyzed. Liver hepcidin was determined by qPCR and ferroportin-1 in liver and spleen was measured by immunoblotting. Dietary fat overload increased adiposity irrespective of dietary Mg levels. Rats fed the high-fat diet, but not those fed the high-fat Mg-restricted diet, had higher spleen Fe concentrations than controls. Weak but significant associations between body adiposity and serum (r = −0.31, P = 0.04) and spleen Fe (r = 0.29, P = 0.04) concentrations were obtained. The unaltered ferroportin-1 expression with low Fe levels suggests increased Fe recycling from spleen to bone marrow due to dietary Mg restriction. A longer study could clarify the consequences of these findings on erythropoiesis and other conditions related to diet-induced obesity.

Whole-body vibration training effect on physical performance and obesity in mice.

The purpose of this study was to verify the beneficial effects of whole-body vibration (WBV) training on exercise performance, physical fatigue and obesity in mice with obesity induced by a high-fat diet (HFD). Male C57BL/6 mice were randomly divided into two groups: normal group (n=6), fed standard diet (control), and experimental group (n=18), fed a HFD. After 4-week induction, followed by 6-week WBV of 5 days per week, the 18 obese mice were divided into 3 groups (n=6 per group): HFD with sedentary control (HFD), HFD with WBV at relatively low-intensity (5.6 Hz, 0.13 g) (HFD+VL) or high-intensity (13 Hz, 0.68 g) (HFD+VH). A trend analysis revealed that WBV increased the grip strength in mice. WBV also dose-dependently decreased serum lactate, ammonia and CK levels and increased glucose level after the swimming test. WBV slightly decreased final body weight and dose-dependently decreased weights of epididymal, retroperitoneal and perirenal fat pads and fasting serum levels of alanine aminotransferase, CK, glucose, total cholesterol and triacylglycerol. Therefore, WBV could improve exercise performance and fatigue and prevent fat accumulation and obesity-associated biochemical alterations in obese mice. It may be an effective intervention for health promotion and prevention of HFD-induced obesity.

Maternal metabolic changes with dietary intake of blueberry during pregnancy and lactation predispose adult progeny to lower mammary tumor growth rate

We have shown the lower growth rates of tumors that developed from Wnt1‐transgenic (Tg) offspring of dams consuming whole blueberry powder (3% BB) during pregnancy and lactation, compared to those of control (Casein) dams. Dietary exposure at post‐weaning through lifetime did not mimic the effects of early BB exposure. The basis for maternal BB effects on mammary tumor growth was examined in dams exposed to BB or control diet as young adults (beginning at age 8 weeks) and throughout pregnancy and lactation. Dams at weaning were evaluated for growth and metabolic parameters. BB‐fed dams had lower abdominal and retroperitoneal fat pad weights than control‐fed dams, although their body weights did not differ. BB dams also displayed increased insulin sensitivity (lower blood glucose, serum insulin, HOMA) and higher serum glutathione and methionine levels. Isolated epithelial cells from pre‐neoplastic mammary tissues of Tg offspring exposed to maternal control and BB diets were analyzed for percentage of basal (CD29highCD24+) and luminal progenitor (CD29lowCD24+) populations. Maternal BB exposure (relative to control) resulted in lower percentage of the luminal subpopulation (6.4% vs 21%), which comprise the tumor bulk in Tg tissues. Results implicate the influence of the favorable metabolic and anti‐oxidative maternal environment with BB diet on developing mammary glands for the improved mammary tumor outcome.Grant Funding Source: USDA‐CRIS 6251–51000‐005–004S, Arkansas Biosciences Institute

Characterisation of the maternal response to chronic phase shifts during gestation in the rat: implications for fetal metabolic programming.

Disrupting maternal circadian rhythms through exposure to chronic phase shifts of the photoperiod has lifelong consequences for the metabolic homeostasis of the fetus, such that offspring develop increased adiposity, hyperinsulinaemia and poor glucose and insulin tolerance. In an attempt to determine the mechanisms by which these poor metabolic outcomes arise, we investigated the impact of chronic phase shifts (CPS) on maternal and fetal hormonal, metabolic and circadian rhythms. We assessed weight gain and food consumption of dams exposed to either CPS or control lighting conditions throughout gestation. At day 20, dams were assessed for plasma hormone and metabolite concentrations and glucose and insulin tolerance. Additionally, the expression of a range of circadian and metabolic genes was assessed in maternal, placental and fetal tissue. Control and CPS dams consumed the same amount of food, yet CPS dams gained 70% less weight during the first week of gestation. At day 20, CPS dams had reduced retroperitoneal fat pad weight (−15%), and time-of-day dependent decreases in liver weight, whereas fetal and placental weight was not affected. Melatonin secretion was not altered, yet the timing of corticosterone, leptin, glucose, insulin, free fatty acids, triglycerides and cholesterol concentrations were profoundly disrupted. The expression of gluconeogenic and circadian clock genes in maternal and fetal liver became either arrhythmic or were in antiphase to the controls. These results demonstrate that disruptions of the photoperiod can severely disrupt normal circadian profiles of plasma hormones and metabolites, as well as gene expression in maternal and fetal tissues. Disruptions in the timing of food consumption and the downstream metabolic processes required to utilise that food, may lead to reduced efficiency of growth such that maternal weight gain is reduced during early embryonic development. It is these perturbations that may contribute to the programming of poor metabolic homeostasis in the offspring.