Retroperitoneal White Adipose Tissue Research Articles

Advanced PamGene Coregulator Interactome Analysis of PPARgamma Reveals that Diet Influences Regulatory Protein Interactions and Signaling Mechanisms

Studies show a strong correlation with type 2 diabetes mellitus (T2DM) in obese patients developing congestive heart failure (CHF) with rosiglitazone treatment. Rosiglitazone, a thiazolidinedione, treats T2DM by improving insulin resistance. Its use has been halted due to a subset of patients developing CHF through unknown mechanisms. Rosiglitazone targets PPARγ, a nuclear receptor highly expressed in adipose tissue and, to a lesser extent, in cardiac tissue. An important mechanism of PPARγ regulation is through coregulators that can alter transcriptional activity through protein-protein interaction to drive PPARγ toward specific pathways. We hypothesized coregulator interaction with PPARγ may regulate its activity differently in adiposity, inducing CHF through adipose-derived peripheral signaling. To address this, we fed 8-week-old C57BL/6 mice a normal chow (NCD) or high-fat (HFD) diet for 16 weeks. Mice were then injected with rosiglitazone every 48 hours for 4 weeks. In NCD and HFD Rosi mice, we found significantly increased heart weights (p-value<0.05) and various weight changes in five adipose depots. To understand the roles of the PPARγ coregulator interactome in adiposity, we used our state-of-the-art PamGene PamStation Nuclear Hormone Receptor chip to measure the interaction of PPARγ with 155 coregulators in five adipose depots and the liver. In adipose depots increasing in weight due to Rosi treatment, such as retroperitoneal white adipose tissue (WAT) and mesenteric WAT, more coregulators associated with the PPARγ complex. Conversely, depots that did not change in weight with Rosi treatment, such as epididymal WAT and inguinal WAT, showed a reduction of coregulators leaving the PPARγ complex, indicating differential PPARγ regulation. Our data suggests that the coregulator interactome of PPARγ in adipose depots represents potential therapeutic targets, and understanding how PPARγ regulation is different in adiposity is crucial to understanding the negative side effects of rosiglitazone treatment. R01DK121797 (T.D.H.) R01DA058933 (T.D.H.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX). We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the gonadotropin releasing hormone (GnRH) antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 wk. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. In addition, rats administered FSH had reduced liver triglyceride concentration (P < 0.001), which correlated with FSH-induced changes at the transcriptomic level. Although not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.NEW & NOTEWORTHY We find no effect of follicle-stimulating hormone (FSH) on energy balance using a novel model in which rats are ovariectomized, subjected to gonadotropin-releasing hormone antagonism, and systematically given back FSH by osmotic pump. However, tissue-specific effects of FSH on adipose tissue and liver were observed in this study. These include unique transcriptomic signatures induced by the hormone and a stark reduction in hepatic triglyceride accumulation.

Egg white hydrolysate protects white adipose tissue against metabolic insult in deoxycorticosterone acetate-salt rats.

The purpose of this study was to investigate the effect of an egg white hydrolysate (EWH) to protect white adipose tissue damage from cardiometabolic changes induced by severe hypertension. Male Wistar rats were uninephrectomised and divided: SHAM (weekly subcutaneous vehicle (mineral oil + propylene glycol, 1:1)), SHAM + EWH (subcutaneous vehicle plus EWH via gavage, 1 g/kg per day), DOCA (deoxycorticosterone acetate diluted in vehicle subcutaneously weekly in subsequent doses of 20 mg/kg -1st week, 12 mg/kg - 2–3th week, and 6 mg/kg -4–8th week, respectively, plus 1 % NaCl and 0·2 % KCl in drinking water), and DOCA + EWH. Body weight gain, food and water intake, glucose and lipid metabolism were evaluated. Oxidative stress was assessed by biochemical assay and immunofluorescence for NOX-1, nuclear factor kappa B (NFκB), and caspase-3 in retroperitoneal white adipose tissue (rtWAT). Proinflammatory cytokines (IL-6 and 1β), CD163+ macrophage infiltration, and immunohistochemistry for TNFα and uncoupling protein-1 were evaluated, as well as histological analysis on rtWAT. Glutathione peroxidase and reductase were also determined in plasma. EWH showed hypocholesterolemic, antioxidant, anti-inflammatory, and anti-apoptotic properties in the arterial hypertension DOCA-salt model. The results demonstrated the presence of functional changes in adipose tissue function by a decrease in macrophage infiltration and in the fluorescence intensity of NFκB, NOX-1, and caspase-3. A reduction of proinflammatory cytokines and restoration of antioxidant enzymatic activity and mitochondrial oxidative damage by reducing uncoupling protein-1 fluorescence intensity were also observed. EWH could be used as a potential alternative therapeutic strategy in the treatment of cardiometabolic complications associated with malignant secondary arterial hypertension.

Dexamethasone Inhibits White Adipose Tissue Browning.

White adipose tissue (WAT) regulates energy balance through energy storage, adipokines secretion and the thermogenesis process. Beige adipocytes are responsible for WAT thermogenesis. They are generated by adipogenesis or transdifferentiation during cold or β3-adrenergic agonist stimulus through a process called browning. Browning has gained significant interest for to its preventive effect on obesity. Glucocorticoids (GCs) have several functions in WAT biology; however, their role in beige adipocyte generation and WAT browning is not fully understood. The aim of our study was to determine the effect of dexamethasone (DXM) on WAT thermogenesis. For this purpose, rats were treated with DXM at room temperature (RT) or cold conditions to determine different thermogenic markers. Furthermore, the effects of DXM on the adipogenic potential of beige precursors and on mature beige adipocytes were evaluated in vitro. Our results showed that DXM decreased UCP-1 mRNA and protein levels, mainly after cold exposure. In vitro studies showed that DXM decreased the expression of a beige precursor marker (Ebf2), affecting their ability to differentiate into beige adipocytes, and inhibited the thermogenic response of mature beige adipocytes (Ucp-1, Dio2 and Pgc1α gene expressions and mitochondrial respiration). Overall, our data strongly suggest that DXM can inhibit the thermogenic program of both retroperitoneal and inguinal WAT depots, an effect that could be exerted, at least partially, by inhibiting de novo cell generation and the thermogenic response in beige adipocytes.

Obesity modulates the cellular and molecular microenvironment in the peritoneal cavity: implication for ovarian cancer risk.

Abdominal obesity increases the risk of developing ovarian cancer but the molecular mechanisms of how obesity supports ovarian cancer development remain unknown. Here we investigated the impact of obesity on the immune cell and gene expression profiles of distinct abdominal tissues, focusing on the peritoneal serous fluid (PSF) and the omental fat band (OFB) as critical determinants for the dissemination of ovarian metastases and early metastatic events within the peritoneal cavity. Female C57BL/6 mice were fed a low-fat (LFD) or a high-fat diet (HFD) for 12 weeks until the body weights in the HFD group were significantly higher and the mice displayed an impaired glucose tolerance. Then the mice were injected with the murine ovarian cancer cells (MOSE-LTICv) while remaining on their diets. After 21 days, the mice were sacrificed, tumor burden was evaluated and tissues were harvested. The immune cell composition of abdominal tissues and changes in gene expression in the PSF and OFB were evaluated by flow cytometry and qPCR RT2-profiler PCR arrays and confirmed by qRT-PCR, respectively. Other peritoneal adipose tissues including parametrial and retroperitoneal white adipose tissues as well as blood were also investigated. While limited effects were observed in the other peritoneal adipose tissues, feeding mice the HFD led to distinct changes in the immune cell composition in the PSF and the OFB: a depletion of B cells but an increase in myeloid-derived suppressor cells (MDSC) and mono/granulocytes, generating pro-inflammatory environments with increased expression of cyto- and chemokines, and genes supporting adhesion, survival, and growth, as well as suppression of apoptosis. This was associated with a higher peritoneal tumor burden compared to mice fed a LFD. Changes in cellular and genetic profiles were often exacerbated by the HFD. There was a large overlap in genes that were modulated by both the HFD and the cancer cells, suggesting that this 'genetic fingerprint' is important for ovarian metastases to the OFB. In accordance with the 'seed and soil' theory, our studies show that obesity contributes to the generation of a pro-inflammatory peritoneal environment that supports the survival of disseminating ovarian cancer cells in the PSF and the OFB and enhances the early metastatic adhesion events in the OFB through an increase in extracellular matrix proteins and modulators such as fibronectin 1 and collagen I expression as well as in genes supporting growth and invasion such as Tenacin C. The identified genes could potentially be used as targets for prevention strategies to lower the ovarian cancer risk in women with obesity.

Combined supplementation with hesperidin, phytosterols and curcumin decreases adiposity and improves metabolic health in ovariectomized rats.

In recent years many women have looked for alternative therapies to address menopause. Hesperidin, phytosterols and curcumin are bioactive compounds that can ameliorate some cardiovascular risk factors associated with menopause, although there are no data concerning the effects of their combined supplementation. We used ovariectomized (OVX) rats, a postmenopausal model with oestrogen deficiency, to evaluate whether supplementation with a multi-ingredient (MI) including hesperidin, phytosterols and curcumin for 57 days would display beneficial effects against fat mass accretion and metabolic disturbances associated with menopause. Twenty OVX rats were orally supplemented with either MI (OVX-MI) or vehicle (OVX). Furthermore, 10 OVX rats orally received the vehicle along with subcutaneous injections of 17β-oestradiol biweekly (OVX-E2), whereas 10 rats were sham operated and received oral and injected vehicles (control group; SH). MI supplementation partly counteracted the fat mass accretion observed in OVX animals, which was evidenced by decreased total fat mass, adiposity index, the weight of retroperitoneal, inguinal and mesenteric white adipose tissue (MWAT) depots and MWAT adipocyte hypertrophy. These effects were accompanied by a significant decrease in the circulating levels of leptin and the mRNA levels of the fatty acid uptake-related genes Lpl and Cd36 in MWAT. These results were very similar to those observed in OVX-E2 animals. OVX-MI rats also displayed a higher lean body mass, lean/fat mass ratio, adiponectin-to-leptin ratio and insulin sensitivity than their OVX counterparts. Our findings can pave the way for using this MI formulation as an alternative therapy to manage obesity and to improve the cardiometabolic health of menopausal women.

Liraglutide modulates morpho-functional and inflammatory gastrointestinal responses in rats.

Obesity impairs homeostatic control of energy and is associated with chronic low-grade inflammation. Effects of glucagon-like peptide-1, the target in the gastrointestinal tract for anti-obesity drugs such as Liraglutide, were not properly associated with inflammation markers. This study investigated the effects of Liraglutide on metabolic and gastrointestinal parameters in a rat model of obesity. Twenty-six Wistar rats with obesity were randomly distributed to receive saline (n = 10), 400 μg (n = 8), or 1200 μg of Liraglutide/kg/day (n = 8), subcutaneously for 30 consecutive days, once a day. Weight gain, feeding efficiency, caloric consumption, gastric motility, adiposity, histomorphometric, murinometric, biochemical parameters and cytokines TNF-α and TGF-β1 in duodenal tissue were measured. Data were analysed by ANOVA, followed by Bonferroni post hoc or Kruskal-Wallis test, followed by Dunn's multiple comparison test. Liraglutide-treated animals had better feeding efficiency and higher caloric intake in a dose-dependent manner. Higher doses slowed gastric emptying and diminished the amplitude of gastric contractions. These effects were accompanied by decreases in intestinal muscle layer thickness and crypt depth. Liraglutide significantly reduced retroperitoneal and visceral white adipose tissue depots. High-dose treatment decreased levels of TNF-α and enhanced levels of TGF-β1 in duodenal tissue. Liraglutide treatment provided significant reductions in total cholesterol, triglyceride and hepatic transaminases. Liraglutide reduced fat accumulation, improved metabolic parameters and downregulated levels of inflammatory signalling in duodenal tissue. Liraglutide at high doses controlled obesity-related outcomes, and such effects seemed to be driven by its action on glucagon-like peptide-1 receptors in the gastrointestinal tract slowing gastric motility.

C-phycocyanin extracted from Spirulina using a green solvent approach presents an anti-obesity characteristic in mice fed a hyperlipidic diet

The effects of C-phycocyanin extract, obtained from Spirulina biomass using a sustainable method with water as solvent, on the white adipose tissue of male mice fed a high-fat diet were evaluated. The normolipid diet and C-phycocyanin groups were similar regarding body mass gain, leptin concentration and phosphorylated protein nuclear factor kappa B p-50 subunit expression. The C-phycocyanin group showed a notable reduction in serum resistin (88.18 ± 31.54, normolipid diet 158.5 ± 52.43) (pg/mL) and the concentration of the pro-inflammatory cytokine tumor necrosis factor alpha (p < 0.05) in 16 weeks of treatment within the retroperitoneal white adipose tissue. The high-fat diet has been associated with obesity development, and the utilization of artificial dyes has been linked to adverse effects. However, C-phycocyanin, a natural pigment, demonstrated promising outcomes. Our findings suggest that the C-phycocyanin extract effectively inhibited body mass gain, regulated leptin and resistin levels, and prevented the increase a pro-inflammatory state.

Adipose Tissue Denervation Blunted the Decrease in Bone Formation Promoted by Obesity in Rats.

The impact of obesity upon bone metabolism is controversial since both beneficial or harmful effects have been reported. Bone remodeling is modulated by the central nervous system through cytokines, hormones and neuromodulators. The present study aimed to evaluate the effects evoked by bilateral retroperitoneal white adipose tissue (rWAT) denervation (Dnx) upon bone mineral metabolism and remodeling in an experimental model of obesity in rats. Male Wistar rats were fed during 18 weeks with high-fat diet (HFD) or standard diet (SD) as controls, and rWAT Dnx or Sham surgery was performed at the 14th week. Biochemical and hormonal parameters, bone histomorphometry, rWAT and hypothalamus protein and gene expression were analyzed. The HFD group presented decreased bone formation parameters, increased serum and bone leptin and FGF23, increased serum and hypothalamic neuropeptide Y (NPY) and decreased serum 1,25-dihydroxyvitamin D3 and PTH. After rWAT Dnx, bone markers and histomorphometry showed restoration of bone formation, and serum and hypothalamic NPY decreased, without alteration in leptin levels. The present study shows that the denervation of rWAT improved bone formation in obese rats mediated by a preferential reduction in neurohormonal actions of NPY, emphasizing the relevance of the adipose tissue-brain-bone axis in the control of bone metabolism in obesity.

Quercetin improves white adipose tissue redox homeostasis in ovariectomized rats.

Estrogen deficiency is a well-known hallmark of menopause and is associated with oxidative stress and metabolic dysfunction. Quercetin (Q), a flavonoid found in fruits and vegetables, has demonstrated anti-inflammatory effects in experimental models of metabolic disorders. In this study, we aimed to investigate the effects of quercetin on retroperitoneal white adipose tissue (rWAT) redox homeostasis and systemic metabolic parameters in ovariectomized (OVX) rats. Female Wistar rats at 3 months old were divided into the following experimental groups: sham-operated treated with vehicle (DMSO 10% + PBS - 1 mL/kg); OVX (vehicle treated) and OVX-Q (25 mg/kg) - via oral gavage, daily for 5 weeks. Q did not prevent weight gain but improved glucose tolerance and blood cholesterol profile, and attenuated uterine atrophy in OVX rats. Furthermore, Q had a protective effect on rWAT, once the OVX-Q group presented lower oxidative stress levels, and reduced levels of the pro-inflammatory cytokine tumor necrosis factor alpha, compared to the OVX group. Q improved antioxidant enzyme activities such as superoxide dismutase and catalase and decreased reactive oxygen species production, in OVX-Q rats. It was followed by increased levels of total thiol content and lower lipid peroxidation. Moreover, Q reduced senescent-related genes p16INK4a and p19ARF expression which were higher in the OVX group. In conclusion, quercetin supplementation improved redox homeostasis and reduced senescence-related markers, and inflammation in rWAT, which was reflected in preserved systemic metabolic health parameters in OVX rats. These findings suggest that quercetin may have therapeutic potential for the management of metabolic disorders associated with menopause-induced estrogen deficiency.

The role of Elateriospermum tapos yoghurt in mitigating high-fat dietary cause of maternal obesity-an experimental study.

Maternal obesity is the key predictor for childhood obesity and neurodevelopmental delay in the offspring. Medicinal plants are considered to be the safe and best option, and at the same time, probiotic consumption during pregnancy provides beneficial effects for both the mother and the child. Current research has shown that Elateriospermum tapos (E. tapos) yoghurt is safe to consume and consists of many bioactive compounds that can exert an anti-obesity effect. Thus, this study has been designed to study the role of E. tapos yoghurt in mitigating maternal obesity. In this study, a total of 48 female Sprague Dawley (SD) rats were assigned to six groups, with eight rats per group, and obesity was induced over 16 weeks with a high-fat diet (HFD) pellet. On the 17th week, the rats were allowed to mate and pregnancy was confirmed through vaginal smear. The obese induced group was further divided into negative and positive control groups, followed by E. tapos yoghurt treatment groups with three different concentrations (5, 50, and 500 mg/kg). The changes in body weight, calorie intake, lipid profile, liver profile, renal profile, and histopathological analysis were measured on postnatal day (PND) 21. The results show that the group with the highest concentration of E. tapos yoghurt (HYT500) supplementation shows gradual reduction in body weight and calorie intake on PND 21 and modulates the lipid level, liver, and renal enzymes to a normal level similar to the normal group. In histological analysis, HYT500 reverses the damage caused by HFD in liver and colon, and reverses the adipocytes' hypertrophy in retroperitoneal white adipose tissue and visceral fat. In conclusion, supplementation of E. tapos yoghurt during the gestational period up to weaning is effective in the gradual weight loss of maternal obese dams from the 500-mg/kg-supplemented group in this study.

Beneficial Effects of Bauhinia rufa Leaves on Oxidative Stress, Prevention, and Treatment of Obesity in High-Fat Diet-Fed C57BL/6 Mice.

Obesity is an epidemic disease worldwide, associated with oxidative stress and the development of several other diseases. Bauhinia rufa (Bong.) Steud. is a native Brazilian Cerrado medicinal plant popularly used for the treatment of obesity. In this context, we investigated the chemical composition of the methanolic extract of B. rufa leaves (MEBr) and evaluated the antioxidant activity and its impact on the prevention and treatment of obesity in mice fed a high-fat diet (HFD 60%). Additionally, the acute oral toxicity of MEBr was evaluated. In MEBr, 17 glycosylated compounds were identified, including myricetin, quercetin, kaempferol, coumaroyl, cyanoglucoside, and megastigmane. In vitro, MEBr showed antioxidant activity in different methods: DPPH•, ABTS•+, FRAP, iron-reducing power, inhibition of β-carotene bleaching, and inhibition of DNA fragmentation. In human erythrocytes, MEBr increased the activities of antioxidant enzymes, superoxide dismutase, and catalase. Under oxidative stress, MEBr reduced oxidative hemolysis, and the malondialdehyde (MDA) levels generated in erythrocytes. Mice treated acutely with MEBr (2000 mg/kg) showed no signs of toxicity. During 90 days, the mice received water or MEBr simultaneously with HFD for induction of obesity. At this stage, MEBr was able to reduce the gain of subcutaneous white adipose tissue (WAT) and prevent the increase of MDA in the heart and brain. After 180 days of HFD for obesity induction, mice that received MEBr simultaneously with HFD (HFD-MEBr) in the last 60 days of treatment (120-180 days) showed a reduction of retroperitoneal and mesenteric WAT deposits and MDA levels in the heart, liver, kidney, and brain, compared to the HFD-Control group. These effects of MEBr were similar to mice treated with sibutramine (HFD-Sibutramine, 2 mg/kg). Combined, the results show that compounds from the leaves of B. rufa affect controlling oxidative stress and actions in the prevention and treatment of obesity. Thus, associated oxidative stress reduction and body composition modulation, in obese people, can contribute to the prevention of obesity-related comorbidities and improve quality of life.

Relationships between rumen microbes, short-chain fatty acids, and markers of white adipose tissue browning during the cold season in grazing Mongolian sheep (Ovisaries)

Mongolian sheep are characteristically cold-tolerant and they partially depend on seasonal browning of white adipose tissue (WAT) to acclimate to cold environments. The present work aimed to examine the rumen microbes, rumen fermentation profile, and relationships between the rumen microbiota, short-chain fatty acids (SCFAs), and markers of WAT browning and are thus conducive to exploring the plateau environment adaptability of Mongolian sheep in the cold season. A comparative analysis of the rumen microbes and SCFAs in the cold and warm seasons was conducted. Rumen microbes were analyzed using Illumina sequencing of the 16S rRNA gene. Ruminal SCFAs were determined by gas chromatography. Spearman's correlation test was used to determine the relationships between the rumen microbiota, SCFAs, and markers of WAT browning. Microbial 16S rRNA sequencing revealed a marked shift in rumen microbiota composition between the two seasons, and the bacteria were characterized by increased levels of the Actinobacteria and genera Christensenellaceae R-7 group, Ruminococcaceae UCG-011, Rikenellaceae RC9 gut group, Papillibacter, and Butyrivibrio 2 and reduced levels of Prevotella 1 and Ruminococcaceae UCG-014 in the cold season (P<0.05). Furthermore, the concentrations of SCFAs such as acetate and butyrate were significantly increased in the cold season (P<0.001 and P<0.05, respectively). Correlation analysis demonstrated that the relative abundances of the Actinobacteria and the genera Christensenellaceae R-7 group, Butyrivibrio 2, Ruminococcaceae UCG-002, and Ruminococcaceae UCG-011, identified as members of the Christensenellaceae, Lachnospiraceae, and Ruminococcaceae families (all within Firmicutes), were positively correlated with markers of browning in either retroperitoneal WAT or perirenal WAT, and acetate was positively correlated with Ruminococcaceae UCG-011 and Butyrivibrio 2 and markers of browning in either retroperitoneal WAT or perirenal WAT. Overall, there are distinct relationships between the rumen microbiota, ruminal SCFAs and markers of WAT browning during the cold season in grazing Mongolian sheep.

Role of white adipose tissue browning in cold seasonal acclimation in grazing Mongolian sheep (Ovisaries)

Mongolian sheep are characteristically cold-tolerant and thus can survive well and maintain genetic stability in the extremely cold environment of the Mongolian Plateau. However, the adaptive mechanism of Mongolian sheep during the cold season in the plateau environment remains unknown. Browning of white adipose tissues (WAT) can trigger nonshivering thermogenesis as a potential strategy to promote an animal's tolerance to cold environments. Thus, a comparative analysis of the genes and proteins of uncoupling protein 1 (UCP1)-dependent and UCP1-independent browning pathways, mitochondrial biogenesis, lipogenic and lipolytic processes of WAT from grazing Mongolian sheep in the cold and warm seasons was conducted. We found seasonal browning of both retroperitoneal WAT and perirenal WAT, and the signalling of the process was mainly transduced by the UCP1- dependent pathway, primarily reflected in the upregulated gene levels of UCP1 and peroxisome proliferative activated receptor gamma coactivator 1 alpha (PGC-1α). In addition, the mean adipocyte diameter and mRNA expression of lipogenic genes in both interscapular WAT and subcutaneous WAT were significantly elevated during the cold season. The findings of this study demonstrate that grazing Mongolian sheep could depend on seasonal browning of both retroperitoneal WAT and perirenal WAT together with the expansion of both interscapular WAT and subcutaneous WAT to acclimate to cold environments of the Mongolian Plateau.

Essential Amino Acids-Rich Diet Decreased Adipose Tissue Storage in Adult Mice: A Preliminary Histopathological Study.

Background: Excess body adipose tissue accumulation is a common and growing health problem caused by an unbalanced diet and/or junk food. Although the effects of dietary fat and glucose on lipid metabolism regulation are well known, those of essential amino acids (EAAs) have been poorly investigated. Our aim was to study the influence of a special diet containing all EAAs on retroperitoneal white adipose tissue (rpWAT) and interscapular brown adipose tissue (BAT) of mice. Methods: Two groups of male Balb/C mice were used. The first was fed with a standard diet. The second was fed with an EAAs-rich diet (EAARD). After 3 weeks, rpWAT and BAT were removed and prepared for subsequent immunohistochemical analysis. Results: EAARD, although consumed significantly less, moderately reduced body weight and BAT, but caused a massive reduction in rpWAT. Conversely, the triceps muscle increased in mass. In rpWAT, the size of adipocytes was very small, with increases in leptin, adiponectin and IL-6 immunostaining. In BAT, there was a reduction in lipid droplet size and a simultaneous increase in UCP-1 and SIRT-3. Conclusions: A diet containing a balanced mixture of free EAA may modulate body adiposity in mice, promoting increased thermogenesis.

L-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold.

The beneficial effects of l-arginine supplementation in obesity and type II diabetes involve white adipose tissue (WAT) reduction and increased substrate oxidation. We aimed to test the potential of l-arginine to induce WAT browning. Therefore, the molecular basis of browning was investigated in retroperitoneal WAT (rpWAT) of rats exposed to cold or treated with 2.25% l-arginine for 1, 3, and 7 days. Compared to untreated control, levels of inducible nitric oxide (NO) synthase protein expression and NO signaling increased in both cold-exposed and l-arginine-treated groups. These increases coincided with the appearance of multilocular adipocytes and increased expression levels of uncoupling protein 1 (UCP1), thermogenic and beige adipocyte-specific genes (Cidea, Cd137, and Tmem26), mitochondriogenesis markers (peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α, mitochondrial DNA copy number), nuclear respiratory factor 1, PPARα and their respective downstream lipid oxidation enzymes after l-arginine treatment. Such browning phenotype in the l-arginine-treated group was concordant with end-course decreases in leptinaemia, rpWAT mass, and body weight. In conclusion, l-arginine mimics cold-mediated increases in NO signaling in rpWAT and induces molecular and structural fingerprints of rpWAT browning. The results endorse l-arginine as a pharmaceutical alternative to cold exposure, which could be of great interest in obesity and associated metabolic diseases.

Panaxnotoginseng extract and total saponin suppress diet-induced obesity and endoplasmic reticulum stress in epididymal white adipose tissue in mice

BackgroundInvestigation on protective effects of Panax notoginseng against obesity and its related mechanisms is incomplete. Present study aimed to investigate the potential anti-obesity effect of the total saponins (PNS) and ethanolic extract of P. notoginseng (PNE).MethodsSix-week-old male C57BL/6J mice received 45% kcal fat diet for 12 weeks to induce obesity. Oral administration of PNS and PNE at 20 mg/kg/day was applied for the last 4 weeks in the obese mice. Lipid profile was determined by ELISA. Histological examination was performed in liver and fat tissues. Protein levels were measured by Western blot.ResultsPNS and PNE did not cause weight loss. PNE but not PNS decreased the mass of epididymal and retroperitoneal white adipose tissue, accompanied by a reduction in adipocyte hypertrophy. PNS and PNE improved lipid profile by reducing the concentrations of triglyceride, total cholesterol and low-density lipoprotein cholesterol in plasma or liver samples. PNS and PNE also relieved fatty liver in obese mice. PNS and PNE inhibited expression and phosphorylation of endoplasmic reticulum (ER) stress-responsive proteins in hypertrophic adipose tissue.ConclusionsPNS and PNE can regulate ER stress-mediated apoptosis and inflammation to alleviate obesity.

Metabolic imprinting induced by a high-sugar diet: effects on microRNA expression and insulin resistance in young rats.

Metabolic imprinting describes associations between nutritional experiences of early life and the development of diseases later in life. The goal of this study was to evaluate the metabolic imprinting induced by a high-sugar diet (HSD) and its effects on microRNA (miRNA) expression and insulin resistance (IR) in young rats. We assessed the effects of expression of adipogenic (miR-200c) and metabolic (miR-126a) miRNAs in retroperitoneal white adipose tissue (rWAT) on IR development. Weaned male Wistar rats (N = 6) were fed a standard chow diet or HSD (68% carbohydrates) for 4-, 8-, or 12-weeks. Serum samples were collected to measure triacylglycerol and VLDL-cholesterol, and we assessed glucometabolic parameters (glucose, insulin, HOMA-IR, and QUICKI). rWAT was collected for microRNA analysis (N = 3). The HSD resulted in body fat accretion and IR after 8-weeks, which resolved by 12-weeks. Moreover, the HSD had a time-dependent effect on miRNA relative expression, downregulating rno-miR-200c-3p at week 8 and rno-miR-126a-3p at week 12. MiR-200 family dysregulation has been related to IR, and miR-126a downregulation could be associated with the improvement in IR observed after a 12-week HSD feeding period. This is the first time that excessive sugar intake post-weaning has been associated with miRNA production by rWAT with an impact on IR development.

Age and sex influence the response in lipid metabolism of dehydrated Wistar rats

Aging is associated a decrease in thirst sensation, which makes old people more susceptible to dehydration. Dehydration produces energy metabolism alterations. Our objective was to determinate the effect of water deprivation (WD) in the lipid metabolism of old male and female rats. Here we show that in the state of WD, aging and sex alters retroperitoneal white adipose tissue (R-WAT) weight of rats, WD old female rats had more lipolysis products than old male rats, a sexual dimorphism in the hormonal response related with metabolism of the adipose tissue of old rats during WD, the expression of P-para mRNA in R-WAT did not present any alteration in animals submitted to WD, the expression of Aqp7 mRNA in R-WAT is altered by WD, age, and sex. Also, WD stimulated an increase in the plasma concentration of oxytocin and the expression of mRNA of the oxytocin receptors in R-WAT.

The Effects of Graded Levels of Calorie Restriction: XVIII.Tissue-Specific Changes in Cell Size and Number in Response to Calorie Restriction.

Calorie restriction (CR) without malnutrition increases the health and life span of diverse taxa. The mechanism(s) behind CR are debated but may be directly linked to body composition changes that maintain energy balance. During a deficit, energy is primarily obtained from white adipose tissue (WAT; utilized) while other tissues remain unchanged (protected) or grow (invested) relative to body mass. The changes in mass of 6 tissues from 48 male C57BL/6 mice following 3-month graded (10%, 20%, 30%, or 40%) CR or fed ad libitum for 12 or 24 hours a day were related to cell size (hypo/hypertrophy) and/or number (hypo/hyperplasia). Tissues studied were retroperitoneal and subcutaneous WAT, brown adipose tissue (BAT; utilized), lungs (protected), and stomach and cecum (invested). Methodology was based on number of nuclei/tissue equaling the number of cells. Extracted DNA was quantified and used to estimate cell numbers (total DNA/DNA per diploid nucleus) and size (tissue mass/nuclei number). WAT utilization was caused solely by hypotrophy whereas BAT utilization resulted from reduced cell number and size. WAT cell size positively correlated with circulating hormones related to energy balance, and BAT cell number and size positively correlated with body temperature. No changes were found in the lungs, consistent with their protected status, whereas hyperplasia appeared to be the dominant mechanism for invested alimentary-tract tissues. These findings indicate the pattern of change of cell size and number across increasing levels of short-term CR is tissue-specific.