Regulation Of Fat Accumulation Research Articles

Cordycepin Ameliorates High Fat Diet-Induced Obesity by Modulating Endogenous Metabolism and Gut Microbiota Dysbiosis.

Numerous metabolic illnesses have obesity as a risk factor. The composition of the gut microbiota and endogenous metabolism are important factors in the onset and progression of obesity. Recent research indicates that cordycepin (CRD), derived from fungi, exhibits anti-inflammatory and antioxidant properties, showing potential in combating obesity. However, further investigation is required to delineate its precise impacts on endogenous metabolism and gut microbiota. In this work, male C57BL/6J mice were used as models of obesity caused by a high-fat diet (HFD) and given CRD. Mice's colon, liver, and adipose tissues were stained with H&E. Serum metabolome analysis and 16S rRNA sequencing elucidated the effects of CRD on HFD-induced obese mice and identified potential mediators for its anti-obesity effects. CRD intervention alleviated HFD-induced intestinal inflammation, improved blood glucose levels, and reduced fat accumulation. Furthermore, CRD supplementation demonstrated the ability to modulate endogenous metabolic disorders by regulating the levels of key metabolites, including DL-2-aminooctanoic acid, inositol, and 6-deoxyfagomine. CRD influenced the abundance of important microbiota such as Parasutterella, Alloprevotella, Prevotellaceae_NK3B31_group, Alistipes, unclassified_Clostridia_vadinBB60_group, and unclassified_Muribaculaceae, ultimately leading to the modulation of endogenous metabolism and the amelioration of gut microbiota disorders. According to our research, CRD therapies show promise in regulating fat accumulation and stabilizing blood glucose levels. Furthermore, through the modulation of gut microbiota composition and key metabolites, CRD interventions have the dual capacity to prevent and ameliorate obesity.

Role of ADAR1 on Proliferation and Differentiation in Porcine Preadipocytes.

Recent research has identified ADAR1 as a participant in the regulation of lipid accumulation in mice. However, there are no reports on the roles of ADAR1 in proliferation, apoptosis and differentiation of porcine preadipocytes. In this study, we investigated the role of ADAR1 in differentiation, proliferation and apoptosis of porcine preadipocytes using CCK-8, EdU staining, cell cycle detection, RT-qPCR, Western blot, a triglyceride assay and Oil Red O staining. The over-expression of ADAR1 significantly promoted proliferation but inhibited the differentiation and apoptosis of porcine preadipocytes. The inhibition of ADAR1 had the opposite effect on the proliferation, differentiation and apoptosis of porcine preadipocytes with over-expressed ADAR1. Then, the regulation mechanisms of ADAR1 on preadipocyte proliferation were identified using RNA-seq, and 197 DEGs in response to ADAR1 knockdown were identified. The MAPK signaling pathway is significantly enriched, indicating its importance in mediating fat accumulation regulated by ADAR1. The study's findings will aid in uncovering the mechanisms that regulate fat accumulation through ADAR1.

Dietary deoxycholic acid decreases fat accumulation by activating liver farnesoid X receptor in grass crap (Ctenopharyngodon idella)

The mechanism underlying the efficacy of different bile acids (BAs) as feed additives to prevent or treat fatty liver disease in cultured fish remains poorly understood. This study compared the effect of different types of BAs on farnesoid X receptor (FXR) activity and lipid accumulation in grass carp. A survey revealed that grass carp (608.24 ± 17.511 g) with severe fatty liver had impaired FXR activity and increased liver total bile acids (TBA) content. In an in vitro study, four typical BAs, chenodeoxycholic acid (CDCA), cholic acid (CA), lithocholic acid (LCA), and deoxycholic acid (DCA), were found to significantly upregulate the expression of FXR and small heterodimer partner (SHP) and decreased lipid droplet accumulation in the hepatocytes of grass carp. Among these, DCA and CDCA exerted the most significant effects. In an in vivo study, grass carp (6.29 ± 0.05 g) were fed 100 mg/kg CDCA, CA, LCA, and DCA for 8 weeks; DCA alone significantly reduced lipid content in the liver and total cholesterol (T-CHO), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDLC) content in the serum. In addition, DCA improved the lipid catabolic activity, inhibited the lipid anabolic activity, and alleviated inflammation in the liver. In contrast, LCA, CDCA, and CA had the opposite effect on these indices. Mechanistically, DCA had a dominant impact on activating FXR in the liver, whereas the other BAs either inhibited gut FXR activity or had the risk in damaging liver cells. In conclusion, our results suggest that different BAs have varying effects on regulating fat accumulation, and DCA appears to be a particularly effective BA in suppressing fat accumulation via FXR pathway activation in the liver of grass crap.

Cardiovascular and lipid-lowering effects of a marine lipoprotein extract in a high-fat diet-induced obesity mouse model.

Obesity is a major health challenge worldwide, with implications for diabetes, hypertension and cardiovascular disease (CVD). Regular consumption of dark-meat fish is linked to a lower incidence of CVD and associated metabolic disorders due to the presence of long-chain omega-3 fatty acid ethyl esters in fish oils. The aim of the present study was to determine whether a marine compound like a sardine lipoprotein extract (RCI-1502), regulates fat accumulation in the heart of a high-fat diet-induced (HFD) mouse model of obesity. To investigate its effects in the heart and liver, we conducted a randomized, 12-week placebo-controlled study in which we analyzed the expression of vascular inflammation markers, obesity biochemical patterns and related CVD pathologies. Male HFD-fed mice treated with a RCI-1502-supplemented diet showed reduced body weight, abdominal fat tissue and pericardial fat pad mass density without systemic toxicity. RCI-1502 significantly reduced triacylglyceride, low-density lipoprotein and total-cholesterol concentrations in serum, but increased HDL-cholesterol levels. Our data show that RCI-1502 is beneficial for reducing obesity associated with a long-term HFD, possibly by exerting a protective effect on lipidic homeostasis, indicated also by histopathological analysis. These results collectively indicate that RCI-1502 acts as a cardiovascular therapeutic nutraceutical agent, which modulates fat-induced inflammation and improves metabolic health.

Frizzled receptors and SFRP5 in lipid metabolism: Current findings and potential applications.

Lipid metabolism plays a very important role as the central metabolic process of the body. Lipid metabolism interruptions may cause many chronic diseases, for example, non-alcoholic fatty liver disease (NAFLD), diabetes, and obesity. Secreted Frizzled Related Protein 5 (SFRP5) and Frizzled receptors (FZD) are two newly discovered adipokines that are involved in lipid metabolism as well as lipogenesis. Both of these adipokines affect lipid metabolism and adipogenesis through three WNT signaling pathways (WNTSP): WNT/β-catenin, WNT/Ca2+, and WNT/JNK. FZD consists of 10 species, which have a cysteine-rich domain (CRD) to bind to the WNT protein for signal transduction. Depending on the type of ligand or co-receptor, they can stimulate or inhibit adipogenesis. In lipid metabolism, they play a role in recognizing fatty acids. In obesity, gene expression of the WNT/FZD receptors is significantly increased. In contrast, SFPR5 serves as an antagonist that can compete with FZD for inhibition of WNTSP. It is believed to have anti-inflammatory potential in obesity and diseases related to abnormal lipid metabolism. In these cases, the expression of SFRP5 is found to be very low leading to the promoted production of proinflammatory cytokines (PICS). Some methods that include using recombinant SFRP5 to improve non-alcoholic steatohepatitis (NASH), using secreted Ly-6/uPAR-related protein 1 (Slurp1) to regulate fat accumulation in the liver through SFRP5, and dietary and lifestyle interventions to improve overweight/obesity have been studied. However, understandings of the molecular mechanisms of these two adipokines and their interactions are very limited. Therefore, more in-depth studies are needed in the future.

Apolipoprotein H: a novel regulator of fat accumulation in duck myoblasts

Apolipoprotein H (APOH) primarily engages in fat metabolism and inflammatory disease response. This study aimed to investigate the effects of APOH on fat synthesis in duck myoblasts (CS2s) by APOH overexpression and knockdown. CS2s overexpressing APOH showed enhanced triglyceride (TG) and cholesterol (CHOL) contents and elevated the mRNA and protein expression of AKT serine/threonine kinase 1 (AKT1), ELOVL fatty acid elongase 6 (ELOVL6), and acetyl-CoA carboxylase 1 (ACC1) while reducing the expression of protein kinase AMP-activated catalytic subunit alpha 1 (AMPK), peroxisome proliferator activated receptor gamma (PPARG), acyl-CoA synthetase long chain family member 1 (ACSL1), and lipoprotein lipase (LPL). The results showed that knockdown of APOH in CS2s reduced the content of TG and CHOL, reduced the expression of ACC1, ELOVL6, and AKT1, and increased the gene and protein expression of PPARG, LPL, ACSL1, and AMPK. Our results showed that APOH affected lipid deposition in myoblasts by inhibiting fatty acid beta-oxidation and promoting fatty acid biosynthesis by regulating the expression of the AKT/AMPK pathway. This study provides the necessary basic information for the role of APOH in fat accumulation in duck myoblasts for the first time and enables researchers to study the genes related to fat deposition in meat ducks in a new direction.

6-OR: Vascular Endothelial ROCK2 Deficiency Promotes Browning and Burning of White Adipose Tissue

The accumulation of visceral fat is associated with multiple coronary risk factors such as glucose intolerance, dyslipidemia, and hypertension. We have previously demonstrated that Rho/Rho-associated protein kinase (ROCK) signaling is activated in animal models of diabetes and is involved in the pathogenesis of vascular complications. Specifically, ROCK is implicated in the molecular basis of inflammation- and ischemia-induced tissue damage through the actions on NF-κB dynamics. These findings support the hypothesis that ROCK signaling could be one of the important therapeutic targets for preventing cardiorenal events. However, isoform-specific roles of ROCKs have not been clarified yet. In this study, we aimed to determine the tissue-intrinsic roles of ROCK2 in the setting of obesity. To this end, we generated vascular endothelium-specific ROCK2 knockout mice (ER2KO) by crossing ROCK2 floxed mice with VE-Cadherin-Cre mice. ER2KO mice were fertile and had the same lifespan as wild type mice. Notably, ER2KO gained weight at a slower rate than wild type mice under high-fat diet feeding. Fat composition, as assessed by magnetic resonance imaging, was significantly lower in ER2KO, even though ER2KO displayed increased food intake. The gene expression analysis revealed increased expression of PPARα, a browning-inducing factor, and its downstream components, CIDEA, IL-4, and IL-10, in white adipose tissue obtained from ER2KO mice. ER2KO mice also showed an elevation in body temperature after fasting, suggesting that endothelial ROCK2 may negatively regulate fat browning. In summary, vascular endothelial ROCK2 negatively regulates fat accumulation through the mechanism of browning inhibition. Disclosure Y. Takeda: None. K. Matoba: None. R. Ukichi: None. Y. Nagai: None. Y. Kanazawa: None. K. Utsunomiya: None. R. Nishimura: Speaker's Bureau; Abbott Diabetes, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck & Co., Inc., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Terumo Corporation. Funding a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science, the MSD Life Science Foundation, the Takeda Science Foundation, the Suzuken Memorial Foundation, Sanofi KK, Tanabe Pharma, and Takeda Pharmaceutical., Kazunori Utsunomiya has received research support from Terumo, Novo Nordisk Pharma, Taisho Pharmaceutical, Böehringer Ingelheim, Kyowa Hakko Kirin, Sumitomo Dainippon Pharma, and OPharmaceutical as, Rimei Nishimura has received speaker honoraria from Astellas Pharma, Nippon Boehringer Ingelheim, Eli Lilly Japan KK, Kissei Pharmaceutical, Medtronic Japan, MSD, Novartis Pharma KK, Novo Nordisk Phar.

Adipocyte-specific deletion of PIP5K1c reduces diet-induced obesity and insulin resistance by increasing energy expenditure

BackgroundPhosphatidylinositol 4-phosphate 5-kinase type I c (PIP5K1c) catalyses the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphorylating phosphatidylinositol 4 phosphate, which plays multiple roles in regulating focal adhesion formation, invasion, and cell migration signal transduction cascades. Here, a new physiological mechanism of PIP5K1c in adipocytes and systemic metabolism is reported.MethodsAdipose-specific conditional knockout mice were generated to delete the PIP5K1c gene in adipocytes. In addition, in vitro research investigated the effect of PIP5K1c deletion on adipogenesis.ResultsDeletion of PIP5K1c in adipocytes significantly alleviated high fat diet (HFD)-induced obesity, hyperlipidaemia, hepatic steatosis, and insulin resistance. PIP5K1c deficiency in adipocytes also decreased adipocyte volume in HFD-induced obese mice, whereas no significant differences were observed in body weight and adipose tissue weight under normal chow diet conditions. PIP5K1c knockout in adipocytes significantly enhanced energy expenditure, which protected mice from HFD-induced weight gain. In addition, adipogenesis was markedly impaired in mouse stromal vascular fraction (SVF) from PIP5K1c-deleted mice.ConclusionUnder HFD conditions, PIP5K1c regulates adipogenesis and adipose tissue homeostasis. Together, these data indicate that PIP5K1c could be a novel potential target for regulating fat accumulation, which could provide novel insight into the treatment of obesity.

Skeletal muscle-secreted myokine interleukin-6 induces white adipose tissue conversion into beige adipose tissue in myostatin gene knockout pigs

Myostatin (MSTN) is primarily expressed in skeletal muscle and plays an important role in the regulation of muscle growth and development as well as fat deposition; however, little is known about the molecular mechanism through which MSTN regulates body fat deposition. Therefore, in this study, we sought to identify the signaling pathways through which MSTN regulates fat accumulation in pigs. MSTN knockout (MSTN−/−) pigs showed increased muscle mass, decreased fat mass, and a leaner body composition. In this study, we found that the adipose tissue of MSTN−/− pigs exhibits the characteristics of beige adipose tissue, and the mRNA expression levels of beige adipose marker genes, including UCP3, Cidea, and CD137, were significantly increased. Remarkably, the observed beige phenotype was not adipocyte autonomous but rather caused by muscle-secreted myokine interleukin (IL)-6. This occurrence results in increased AMP-activated protein kinase (AMPK) phosphorylation in adipose tissue, which subsequently activates peroxisome proliferator-activated receptor gamma coactivator 1α and the conversion of white adipocytes to beige in pigs. Therefore, we concluded that MSTN deficiency leads to increased IL-6 secretion in skeletal muscle and activates AMPK in adipocytes, thereby increasing the beige adipose tissue in MSTN−/− pigs.

Baicalin attenuates diet-induced obesity partially through promoting thermogenesis in adipose tissue

BackgroundAdipose tissues have essential roles on energy homeostasis and the development of metabolic syndrome and obesity, they have become critical targets for treating obesity and metabolic disorders. Baicalin is a flavonoid that derived from the root of Scutellaria baicalensis, and it has been reported to take part in the regulation of adipocyte function. All these highlighted the potential of baicalin in the regulation of fat accumulation and obesity. Yet the impact of baicalin on thermogenic function of adipocytes remains to be deciphered. ObjectiveThis study aims to explore the anti-obesity effects of baicalin. Materials & MethodsThe level of mRNA was detected by qRT-PCR and the protein expression level was examined by western blot. H&E staining was used for the observation of the structure of adipose tissue. Serum triglyceride and insulin levels were detected by commercial test kits. ResultsOur data demonstrated that baicalin up-regulates the expression of UCP1 and PGC1a in a dose-dependent manner in vitro. Baicalin also increases ERK phosphorylation, and the increased expression of UCP1 and PGC1a in adipocytes could be inhibited by an ERK inhibitor, U0126. Moreover, dietary baicalin ameliorates high fat diet (HFD)-induced obesity without affecting food intake. In addition, dietary baicalin inhibits adipocyte hypertrophy and enhances thermogenic gene program in sWAT and intrascapular brown adipose tissue (iBAT) in vivo. Discussion & ConclusionBaicalin prevents HFD-induced obesity partially through promoting adipocyte thermogenesis. Baicalin may be a promising compound against human obesity and related metabolic diseases.

FXR Regulates Adipose Tissue Remodeling during Obesity

Obesity is a major epidemic and results in adipose tissue expansion and dysregulated glucose and lipid metabolism. Farnesoid X receptor (FXR) is a nuclear receptor expressed in many tissues that transcriptionally regulates energy homeostasis. However, the role of FXR in adipose tissue remains elusive. We identified Fxr expression in adipocytes isolated from both white (WAT) and brown (BAT) adipose tissues, and uncovered that adipocyte-specific Fxr knockout (Ad-FxrKO) mice recently generated in our laboratory exhibit adipocyte hypertrophy and concomitant reductions in lipolysis and the expression of lipolytic genes in both white and brown fat depots, which is correlated with ectopic fat accumulation in the liver and systemic glucose intolerance when challenged with a 60% high fat diet (HFD) or high fat/high sucrose western diet. Further, transcriptomic analysis of WAT from Ad-FxrKO and control mice upon chow or HFD revealed that many genes enriched in pathways associated with lipid and glucose homeostasis are misregulated in Ad-FxrKO mice with distinct patterns under normal and obese conditions. These data suggest that adipocyte-specific FXR may play a crucial role in regulating fat accumulation and the subsequent glucose homeostasis during diet-induced obesity. In addition to the energy storage and distribution properties of adipose tissue, BAT has high mitochondrial content and burns energy to produce heat and combat obesity. We found that Ad-FxrKO mice display reductions in energy expenditure and the expression of mitochondrial genes, revealing a key role of FXR in controlling BAT mitochondrial function and the consequent thermogenesis. Overall, we demonstrate that FXR can control fat breakdown and regulate mitochondrial functions in the adipose tissue, which in turn, modulates whole-body lipid and glucose metabolism.

Caenorhabditis elegans as a model organism in obesity research.

Obesity is a global health problem associated with many comorbidities such as type 2 diabetes and cancer. The number of individuals with overweight and obesity have increased dramatically within the past few years. Given the worldwide cost of an obesity pandemic, it is crucial to understand molecular pathways and identify novel factors that regulate fat storage in humans. In recent years, Caenorhabditis elegans has been widely used to investigate metabolic and neuroendocrine mechanisms involved in the regulation of energy metabolism. In this review, we describe similarities in fundamental signalling pathways regulating fat accumulation between nematodes and mammals. Like in humans, fat storage in C. elegans depends on the interaction of genetic and environmental factors such as diet, microbiota and ambient temperature. Despite many challenges, the simplicity of use, relatively short lifespan, genetic conservation and availability of many valuable experimental techniques make C. elegans an attractive and useful model organism in obesity research.

MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance

Obese individuals are more susceptible to comorbidities than individuals of healthy weight, including cardiovascular disease and metabolic disorders. MicroRNAs are a class of small and noncoding RNAs that are implicated in the regulation of chronic human diseases. We previously reported that miR-125b plays a critical role in adipogenesis in vitro. However, the involvement of miR-125b-2 in fat metabolism in vivo remains unknown. In the present study, miR-125b-2 knockout mice were generated using CRISPR/CAS9 technology, resulting in mice with a 7 bp deletion in the seed sequence of miR-125b-2. MiR-125b-2 knockout increased the weight of liver tissue, epididymal white fat and inguinal white fat. MiR-125b-2 knockout also increased adipocyte volume in HFD-induced obese mice, while there were no significant differences in body weight and feed intake versus mice fed a normal diet. Additionally, qRT-PCR and western blot analysis revealed that the expression of the miR-125b-2 target gene SCD-1 and fat synthesis-associated genes, such as PPARγ and C/EBPα, were significantly up-regulated in miR-125b-2KO mice (P < 0.05). Moreover, miR-125b-2KO altered HFD-induced changes in glucose tolerance and insulin resistance. In conclusion, we show that miR-125b-2 is a novel potential target for regulating fat accumulation, and also a candidate target to develop novel treatment strategies for obesity and diabetes.

FSH promotes fat accumulation by activating PPARγ signaling in surgically castrated, but not immunocastrated, male pigs

Follicle-stimulating hormone (FSH) was recently implicated as a novel regulator of fat accumulation. Surgical castration causes high FSH concentrations and increases fat accumulation, whereas immunocastration results in low FSH concentrations and less fat in immunocastrated boars versus barrows. However, detailed information regarding the role of FSH in regulation of fat accumulation in male pigs is unclear. First, expression of FSH receptor was confirmed (real-time quantitative PCR) in subcutaneous and visceral adipose tissues (SAT and VAT, respectively) of boars. Then, surgical castration (high FSH model) was compared to immunocastration (low FSH model) to investigate potential roles of FSH in adipogenesis and fat accumulation. High FSH concentrations after surgical castration activated PPARγ signaling by upregulating expression of CREB (P < 0.05), and then recruited an array of PPARγ target adipogenic genes, including transcription factor (C/EBPα), long-chain fatty acid uptake (LPL), fatty acid de novo synthesis (FASN, ACACA) and lipid droplet formation (PLIN1) in both SAT and VAT, promoting fat accumulation in barrows. In contrast, much lower serum FSH concentrations in immunocastrates attenuated (P < 0.05) expressions of PPARγ and PPARγ target genes in both SAT and VAT, resulting in less fat accumulation in immunocastrated boars versus barrows. We concluded that the substantially elevated FSH concentrations in barrows promoted fat accumulation by activating the PPARγ signaling pathway in adipose tissues, whereas immunocastrates accumulated less fat due to low FSH.

FXR regulates metabolic function of fat depots during obesity

Obesity is a major epidemic and is associated with excess calorie intake leading to adipose tissue expansion and metabolic dysfunction. Farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates lipid and glucose metabolism. Despite several studies revealing FXR expression in the adipose tissue, its exact role in this tissue remains elusive. We determined that both primary pre‐ and post‐differentiated adipocytes from inguinal white (WAT) and brown (BAT) adipose tissue express Fxr transcripts. Notably, adipose‐specific Fxr knockout (Ad‐FxrKO) mice recently generated in our laboratory exhibit glucose intolerance, increased fat accumulation and concomitant reduction in the expression of lipolytic genes in both WAT and BAT when challenged with a high‐fat diet. These data suggest that adipose‐specific FXR may play a crucial role in regulating fat accumulation and subsequent glucose homeostasis during diet‐induced obesity. Since BAT is specialized for non‐shivering thermogenesis by generating heat through uncoupled mitochondrial respiration, we investigated the role for FXR in brown adipocyte mitochondrial function. We found that when Fxr is deleted, genes involved in BAT mitochondrial β‐oxidation, biosynthesis and respiratory chain complex are down‐regulated. Conversely, FXR activation by its endogenous bile acid ligand, chenodeoxycholic acid increases mitochondrial membrane potential of primary differentiated brown adipocytes in vitro, suggesting a key role for FXR in controlling brown adipocyte mitochondrial function and a potential role in thermogenesis. Overall, we demonstrate that FXR can modulate fat break down and regulate mitochondrial functions in the adipose tissue.Support or Funding InformationSupported by R01 DK113080 from NIDDK, and UIUC Start Up Funds.

Ellagic Acid and Urolithins A and B Differentially Regulate Fat Accumulation and Inflammation in 3T3-L1 Adipocytes While Not Affecting Adipogenesis and Insulin Sensitivity.

Ellagic acid (EA) is a component of ellagitannins, present in crops such as pecans, walnuts, and many berries, which metabolized by the gut microbiota forms urolithins A, B, C, or D. In this study, ellagic acid, as well as urolithins A and B, were tested on 3T3-L1 preadipocytes for differentiation and lipid accumulation. In addition, inflammation was studied in mature adipocytes challenged with lipopolysaccharide (LPS). Results indicated that EA and urolithins A and B did not affect differentiation (adipogenesis) and only EA and urolithin A attenuated lipid accumulation (lipogenesis), which seemed to be through gene regulation of glucose transporter type 4 (GLUT4) and adiponectin. On the other hand, gene expression of cytokines and proteins associated with the inflammation process indicate that urolithins and EA differentially inhibit tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Urolithins A and B were found to reduce nuclear levels of phosphorylated nuclear factor κB (p-NF-κB), whereas all treatments showed expression of nuclear phosphorylated protein kinase B (p-AKT) in challenged LPS cells when treated with insulin, indicating the fact that adipocytes remained insulin sensitive. In general, urolithin A is a compound able to reduce lipid accumulation, without affecting the protein expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (c/EBPα), and PPARα, whereas EA and urolithin B were found to enhance PPARγ and c/EBPα protein expressions as well as fatty acid (FA) oxidation, and differentially affected lipid accumulation.

Low and high concentrations of butyrate regulate fat accumulation in chicken adipocytes via different mechanisms

ABSTRACT The present study investigated the effects of varying concentrations of sodium butyrate (SB) on fat accumulation and cell proliferation in chicken adipocytes. High and low serial concentrations of SB used significantly reduced adipocytic fat accumulation. However, they were observed to exhibit differences in cell morphology and distinctions in lipogenic genes expression profiles. At lower concentration (0.01 mM), fat accumulation was decreased with an associated downregulation in the expression of lipogenic genes, which was mediated by free fatty acid receptors (FFARs). Contarily, at higher concentration (1 mM), the fat droplets laden in adipocytes were enlarged, and this was accompanied with activation of lipogenic genes expression. However, the total accumulated fat was also decreased largely due to reduction in cell numbers, which was partially attributable to the reduction in histone deacetylase (HDAC) activity. Animal experiments further indicated that dietary supplementation of lower dose coated SB (0.1% wt/wt) inhibited fat deposition in livers and abdominal fat tissues of broilers, suggesting the potential application of sodium butyrate as feed additive in the regulation of fat deposition.

The Inhibitory Effect of Betanin on Adipogenesis in 3T3-L1 Adipocytes

Betanin, a natural pigment that presents ubiquitously in plants, has been reported to show biological effects. However, not much is known on the effectiveness of betanin in regulating fat accumulation. Therefore, the aim of this study is to explore the inhibitory effect of betanin on adipogenesis in 3T3-L1 adipocytes and its mechanism action. The results show betanin significantly inhibited oil red O-stained material (OROSM) and triglyceride levels in 3T3-L1 adipocytes, indicating betanin inhibited lipid accumulation in 3T3-L1 adipocytes. In addition, the peroxisome proliferator–activated receptor γ (PPARγ) expression was significantly inhibited in the betanin-treated adipocytes, implying that betanin suppressed the cellular PPARγexpression in 3T3-L1 adipocytes. Moreover, the suppression of lipid accumulation by betanin occurred by decreasing the gene expression of PPARγ, CCAAT-enhancer-binding protein α (C/EBPα) and sterol regulatory element binding protein 1c (SREBP-1c). Taken together, these findings suggest betanin may be a mediator of adipocyte accumulation, leading to the inhibition of lipogenesis in 3T3-L1 adipocytes and betanin is therefore potentially useful for designing new antiadipogenic agent.

Gut microbiota: a new path to treat obesity.

Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/- bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss.

Pannexin 1 and Pannexin 3 regulate body fat accumulation in mouse models of dietinduced obesity

Pannexins (Panx) are channel‐forming glycoproteins important in paracrine signaling and cellular development. Panx1 and Panx3 are expressed in adipocytes and adipose stromal cells. We discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet, while Panx3 KO mice have reduced total fat mass and weigh less than WT controls. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain but showed an increase in glucose and insulin levels compared to WT. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory activity, and reduced sleep duration relative to their WT littermates on a high‐fat diet. To uncover the cellular mechanism responsible for the increased fat content in the Panx1 KO, we isolated primary cultures of adipose‐derived stromal cells (ASCs) from WT and KO fat pads. In WT ASCs we observed that Panx1 protein levels increase upon induction into an adipogenic lineage. ASCs isolated from Panx1 KO mice proliferate less but demonstrate enhanced adipogenic differentiation with increased intracellular lipid accumulation, glycerol‐3‐phosphate dehydrogenase (GPDH) enzyme activity, and adipokine secretion, as compared to WT ASCs. This was consistent with the increased adipocyte size (hypertrophy) and decreased adipocyte numbers observed in subcutaneous fat of the Panx1 KO mice compared to WT. Panx3 is also expressed in adipose stromal cells and Panx3 protein levels significantly increase in differentiated adipocytes. However, the effect of the Panx3 KO seems to be the opposite of the Panx1 KO, with decreased weight under a high fat diet and lower fat mass (even under a normal chow diet). We propose that Panx1 and Panx3 may play opposing roles in adipose stromal cells during the early stages of adipogenic proliferation and differentiation, regulating fat accumulation in vivo.Support or Funding InformationFunded by the Canadian Institutes of Health Research (CIHR) grants to SP and LFThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.