Expression Of Lipolytic Genes Research Articles

Glycyrrhizic acid suppresses early stage of adipogenesis through repression of MEK/ERK-mediated C/EBPβ and C/EBPδ expression in 3T3-L1 cells

Glycyrrhizic acid (GA), a major constituent of the root of licorice (Glycyrrhiza glabra), and has various biological activities, including anti-obesity property. However, the molecular mechanism of anti-adipogenic effect of GA is still unclear. In this study, we investigated the anti-adipogenic effects of GA in mouse adipocytic 3T3-L1 cells and elucidated its underlying molecular mechanism. GA decreased the intracellular triglyceride level. The expression levels of the adipogenic and lipogenic genes were lowered by treatment with GA in a concertation-dependent manner. In contrast, GA did not affect the lipolytic gene expression and the released glycerol level. GA suppressed the early stage of adipogenesis when it was added for 0–3 h after initiation of adipogenesis. Moreover, GA reduced the mRNA levels of CCAAT/enhancer binding protein (C/EBP) β and C/EBPδ, both of which activate the early stage of adipogenesis. Furthermore, GA decreased phosphorylation of extracellular signal-regulated kinase [ERK: p44/42 mitogen-activated protein kinase (MAPK)] in the early stage of adipogenesis. In addition, a MAPK kinase (MEK) inhibitor, PD98059 reduced the C/EBPβ and C/EBPδ gene expression. These results indicate that GA suppressed the early stage of adipogenesis through repressing the MEK/ERK-mediated C/EBPβ and C/EBPδ expression in 3T3-L1 cells. Thus, GA has an anti-adipogenic ability and a possible agent for treatment of obesity.

Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis.

How regular physical activity is able to improve health remains poorly understood. The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing muscle-specific miR-1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR-1 promoted adrenergic signaling and lipolysis by targeting Tfap2α, a known repressor of Adrβ3 expression. Inhibiting EV release prevented the MOV-induced increase in eWAT miR-1 abundance and expression of lipolytic genes. Resistance exercise decreased skeletal muscle miR-1 expression with a concomitant increase in plasma EV miR-1 abundance, suggesting a similar mechanism may be operative in humans. Altogether, these findings demonstrate that skeletal muscle promotes metabolic adaptations in adipose tissue in response to MOV via EV-mediated delivery of miR-1.

Effects of Cetobacterium somerae fermentation product on gut and liver health of common carp (Cyprinus carpio) fed diet supplemented with ultra-micro ground mixed plant proteins

Improving the replacement percentage of fish meal by plant proteins is of value for the aquaculture industry. Cetobacterium is the dominant commensal bacterium in many fish species. However, the function and potential beneficial effects of Cetobacterium is unknown. In this study, carps were fed with a practical basal diet with partial fish meal replacement by plant proteins (Control), basal diet with improved fish meal replacement percentage by adding ultra-micro ground mixed plant proteins (uPP), or the uPP diet supplemented with the fermentation product of a commensal bacterial strain Cetobacterium somerae XMX-1 (uPP + XMX-1). The effects of C. somerae XMX-1 fermentation product on gut and liver health of carp fed uPP supplemented diet were evaluated. After 4-week feeding, growth performance, feed utilization, biometric parameters, inflammatory score, expression of inflammation-related and lipid metabolism related genes were evaluated. The levels of LBP, LPS, AST and ALT in serum were assessed. 16S rRNA gene pyrosequencing was used to evaluate intestinal microbiota. Results showed that dietary uPP and uPP + XMX-1 had no effect on survival rate and growth (p > 0.05). However, dietary uPP compromised gut and liver health of fish. The expressions of inflammation related genes in gut and liver and the levels of LBP, LPS, AST and ALT in serum were significantly increased in uPP group versus control (p < 0.05). Interestingly, uPP + XMX-1 significantly decreased the expressions of inflammation related genes in gut and liver, as well as the levels of LBP, LPS, AST and ALT in serum compared to the uPP group (p < 0.05). In addition, uPP + XMX-1 significantly reduced the formation of lipid droplets in liver and significantly up-regulated the expression of lipogenesis genes and down-regulated the expression of lipolysis genes (p < 0.05) in comparison to the uPP group. Taken together, our study suggests that dietary uPP can impair gut and liver health and induce fatty liver, whereas C. somerae XMX-1 fermentation product can improve gut and liver health of common carp and decrease lipid deposition in liver, suggesting that XMX-1 fermentation product can be used as feed additive to improve the efficacy of fish meal replacement by plant proteins.

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.

Selective Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Attenuates High-Fat Diet-Induced Hepatic Steatosis in Mice.

IntroductionThe effect of 11β-hydroxysteroid dehydrogenase type1 (11β-HSD1) inhibition on hepatic steatosis is incompletely understood. Here, we aimed to determine the therapeutic effect of BVT.2733, a selective 11β-HSD1 inhibitor, on hepatic steatosis.Materials and MethodsC57B/6J mice were randomly divided into a low-fat diet (LFD) fed group and a high-fat diet (HFD) fed group. Mice were fed with HFD for 28 weeks which induced obesity and severe hepatic steatosis. The two groups were further divided into four groups as follows: LFD, LFD with BVT.2733, HFD, and HFD with BVT.2733. Mice in LFD+BVT and HFD+BVT groups were intraperitoneally injected with BVT.2733 daily for 30 days. Effects of BVT.2733 on mice body weight, serum lipid profile, serum free fatty acids (FFAs), glucocorticoid levels, gene expression in adipose and liver tissues were assessed.ResultsInjection of a low dose of BVT.2733 (50 mg/kg/day) reduced body weight and hyperlipidemia, but did not improve glucose tolerance and insulin resistance in diet-induced obese mice. The low dose of BVT.2733 attenuated hepatic steatosis, liver injury, and liver lipolytic gene expression in diet-induced obese mice. Besides, the low dose of BVT.2733 reduced fat mass and lipolysis in visceral adipose tissues, hepatic FFAs, and serum corticosterone levels in diet-induced obese mice.ConclusionOur study shows that moderate inhibition of 11β-HSD1 by BVT.2733 reduces FFAs and corticosterone synthesis in fatty tissues, thereby attenuates the delivery of corticosterone and FFAs to the liver. Collectively, this prevents high-fat diet-induced hepatic steatosis.

Secoisolariciresinol Diglucoside Regulates Adipose Tissue Metabolic Disorder in Obese Mice Induced by a Western Diet

Secoisolariciresinol diglucoside (SDG) is the main component of flax lignans. Current studies have reported a positive effect of SDG on obesity and metabolic diseases. SDG has strong blood fat- and blood sugar-lowering, anti-inflammatory, and antioxidant effects and prevents heart disease and other chronic diseases. In this study, we explored the effects of SDG on Western diet-induced obesity and lipid metabolic disorder. Supplementing Western diet-induced obese mice with 40 mg kg1 d1, SDG for 12 weeks significantly reduced body and tissue weights. Increased adiponectin levels and decreased serum leptin and resistin levels were observed in obese mice orally administered SDG. Proliferation of adipose tissue was observed by hematoxylin and eosin staining, and cell size was quantitatively analyzed. As a result, SDG inhibited the proliferation of adipose tissue. In addition, SDG suppressed the mRNA expression of lipid synthetic genes and upregulated the mRNA expression of lipolytic genes. Overall, these results indicate that SDG inhibits obesity induced by a Western diet and regulates adipose tissue metabolic disorder. These results provide a theoretical basis for further study on the regulation of obesity and lipid metabolic disorder caused by SDG.

Sex Hormone Binding Globulin (SHBG) Mitigates ER Stress in Hepatocytes In Vitro and Ex Vivo.

Despite multiple research studies regarding metabolic syndrome and diabetes, the full picture of their molecular background and pathogenies remains elusive. The latest studies revealed that sex hormone-binding globulin (SHBG)—a serum protein released mainly by the liver—may participate in metabolic dysregulation, as its low serum level correlates with a risk for obesity, metabolic syndrome, and diabetes. Yet, the molecular phenomenon linking SHBG with these disorders remains unclear. In the presented study, we investigate how exogenous SHBG affects metabolically impaired hepatocytes with special attention to endoplasmic reticulum stress (ER stress) and lipid metabolism both in vitro and ex vivo. For that reason, palmitate-treated HepG2 cells and liver tissue samples collected post mortem were cultured in the presence of 50 nM and 100 nM SHBG. We found that SHBG protects against ER stress development and its progression. We have found that SHBG decreased the expression levels of inositol-requiring enzyme 1 (IRE1α), activating transcription factor 6 (ATF6), DNA damage-inducible transcript 3 (CHOP), and immunoglobulin heavy chain-binding protein (BIP). Furthermore, we have shown that it regulates lipolytic gene expression ex vivo. Additionally, herein, we deliver a novel large-animal model to study SHBG in translational research. Our data provide new insights into the cellular and molecular mechanisms by which SHBG modulates hepatocyte metabolism and offer a new experimental approach to study SHBG in human diseases.

Effects of Ginsenoside Rg3 on Inhibiting Differentiation, Adipogenesis, and ER Stress-Mediated Cell Death in Brown Adipocytes.

Objectives Ginsenoside Rg3 (Rg3), a main active component of Panax ginseng, has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes. Methods The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored. Results Rg3 significantly induced cytotoxicity in differentiated MPBAs but not in undifferentiated MPBAs. Rg3 treatment downregulated the expression of differentiation and adipogenesis markers and the level of perilipin in MPBAs while upregulating the expression of lipolytic Kruppel-like factor genes. Rg3 also induced lipolysis and efflux of triglycerides from MPBAs and subsequently increased proinflammatory cytokine levels. Notably, Rg3 treatment resulted in elevation of ER stress and proapoptotic markers in MPBAs. Conclusions Our results demonstrate that Rg3 is able to selectively exert cytotoxicity in differentiated MPBAs while leaving undifferentiated MPBAs intact, resulting in the induction of ER stress and subsequent cell death in MPBAs via regulation of various genes related to adipocyte differentiation, adipogenesis, lipolysis, and inflammation. These results indicate that further studies on the potential therapeutic applications of Rg3 are warranted.

CL316243 treatment mitigates the inflammation in white adipose tissues of juvenile adipocyte-specific Nfe2l1 knockout mice

Nuclear factor-erythroid 2-related factor 1 (NFE2L1) is a key transcription factor that regulates cellular adaptive responses to various stresses. Our previous studies revealed that adult adipocyte-specific Nfe2l1-knockout [Nfe2l1(f)-KO] mice show adipocyte hypertrophy and severe adipose inflammation, which can be worsened by rosiglitazone, a peroxisome proliferator-activated receptor γ agonist. To further assess the crucial roles of NFE2L1 in adipocytes, we investigated the effect of CL316243, a β3 adrenergic agonist that promotes lipolysis via a post-translational mechanism, on adipose inflammation in juvenile Nfe2l1(f)-KO mice. In contrast to adult mice, 4-week-old juvenile Nfe2l1(f)-KO mice displayed a normal fat distribution but reduced fasting plasma glycerol levels and elevated adipocyte hypertrophy and macrophage infiltration in inguinal and gonadal WAT. In addition, Nfe2l1(f)-KO mice had decreased expression of multiple lipolytic genes and reduced lipolytic activity in WAT. While 7 days of CL316243 treatment showed no significant effect on adipose inflammation in Nfe2l1-Floxed control mice, the same treatment dramatically alleviated macrophage infiltration and mRNA expression of inflammation and pyroptosis-related genes in WAT of Nfe2l1(f)-KO mice. Together with previous findings in adult mice, the current study highlights that NFE2L1 plays a fundamental regulatory role in lipolytic gene expression and thus might be an important target to improve adipose plasticity and lipid homeostasis.

Anti-Adipogenic Polyacetylene Glycosides from the Florets of Safflower (Carthamus tinctorius).

Safflower (Carthamus tinctorius) is an annual herb belonging to the Compositae family; it has a history of use as a food colorant, dye, and medicine in oriental countries. LC-MS-UV-based chemical analysis of extract of the florets of C. tinctorius led to the isolation of two new C10-polyacetylene glycosides, (8Z)-decaene-4,6-diyne-1,10-diol-1-O-β-d-glucopyranoside (1) and (8S)-deca-4,6-diyne-1,8-diol-1-O-β-d-glucopyranoside (2), together with five known analogs (3–7). The structures of the new compounds were determined by using 1D and 2D NMR spectroscopic data and HR-MS data, as well as chemical transformations. Of compounds 1–7, compounds 2, 3, and 4 inhibited the adipogenesis of 3T3-L1 preadipocytes, whereas compounds 1 and 6 promoted adipogenesis. Compounds 2, 3, and 4 also prevented lipid accumulation through the suppression of the expression of lipogenic genes and the increase of the expression of lipolytic genes. Moreover, compounds 3 and 4 activated AMPK, which is known to facilitate lipid metabolism. Our findings provide a mechanistic rationale for the use of safflower-derived polyacetylene glycosides as potential therapeutic agents against obesity.

Multigenerational study of the obesogen effects of bisphenol S after a perinatal exposure in C57BL6/J mice fed a high fat diet.

Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue. We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice. Pregnant C57BL6/J mice were exposed to BPS (1.5μg/kgbw/day ie a human equivalent dose of 0.12μg/kgbw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed. In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females. BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females.

L-carnitine exerts a nutrigenomic effect via direct modulation of nuclear receptor signaling in adipocytes, hepatocytes and SKMC, demonstrating its nutritional impact

L-carnitine is an indispensable metabolite facilitating the transport of fatty acids into the mitochondrial matrix and has been previously postulated to exert a nutrigenomic effect. However, the underlying molecular mechanisms remain mostly unclear. We hypothesized that L-carnitine interacts with nuclear receptors involved in metabolic regulation, thereby modulating downstream targets of cellular metabolism. Therefore, we investigated the effect of L-carnitine supplementation on protein activity, mRNA expression, and binding affinities of nuclear receptors as well as mRNA expression of downstream targets in skeletal muscle cells, hepatocytes, and differentiated adipocytes. L-carnitine supplementation to hepatocytes increased the protein activity of multiple nuclear receptors (RAR, RXR, VDR, PPAR, HNF4, ER, LXR). Diverging effects on the mRNA expression of PPAR-α, PPAR-δ, PPAR-γ, RAR-β, LXR-α, and RXR-α were observed in adipocytes, hepatocytes, and skeletal muscle cells. mRNA levels of PPAR-α, a key regulator of lipolysis and β-oxidation, were significantly upregulated, emphasizing a role of L-carnitine as a promoter of lipid catabolism. L-carnitine administration to hepatocytes modulated the transcription of key nuclear receptor target genes, including ALDH1A1, a promoter of adipogenesis, and OGT, a contributor to insulin resistance. Electrophoretic mobility shift assays proved L-carnitine to increase binding affinities of nuclear receptors to their promoter target sequences, suggesting a molecular mechanism for the observed transcriptional modulation. Overall, these findings indicate that L-carnitine modulates the activity and expression of nuclear receptors, thereby promoting lipolytic gene expression and decreasing transcription of target genes linked to adipogenesis and insulin resistance.

Dietary Lactobacillus acidophilus and Mannan-Oligosaccharides Alter the Lipid Metabolism and Health Indices in Broiler Chickens.

The effects of dietary Lactobacillus acidophilus (LBA) and mannan-oligosaccharide (MOS) supplementation on lipid metabolism and consequent lipid profile and health indices in broiler chicken were investigated in this study. Supplementation of 0.2% MOS along with either 106 or 107 LBA/g feed in broiler chicken downregulated hepatic expression of genes involved in lipogenesis, and upregulated expression of lipolytic genes. It caused decline of lipogenesis and increase of lipid oxidation which resulted in lower carcass fat content. None of the genes studied influenced fatty acid profile of chicken meat except the expression of stearoyl CoA (Δ9) desaturase-1 (SCD-1) whose upregulation increased monounsaturated fatty acid (MUFA) content at the cost of saturated fatty acid (SFA) content. The lipid metabolism indices of chicken meat such as ∆9 desaturase index (DI) increased in birds supplemented with 0.2% MOS along with either 106 or 107CFU LBA/g feed, whereas no effect was observed on ∆5+∆6 DI. The supplementation of 0.2% MOS along with either 106 or 107CFU LBA/g feed in birds improved the health indices of chicken meat due to upregulation of SCD-1 expression. The supplementation of 0.2% MOS along with either 106 or 107CFU LBA/g feed in broiler chicken produced hypocholesterolemic and hypolipidemic effects with improved serum cardio-protective indices.

HFD and HFD-provoked hepatic hypoxia act as reciprocal causation for NAFLD via HIF-independent signaling

BackgroundThe occurrence of non-alcoholic fatty liver disease (NAFLD) is found to be higher in patients with obstructive sleep apnea (OSA), which is characterized by intermittent hypoxia. Activation of hypoxia-inducible factors has been shown in the development and progression of NAFLD, implying a cause and effects relationship between NAFLD and hypoxia. The present study was designed to investigate the interaction of lipotoxicity and hypoxia in the pathogenesis of NAFLD using mice model with high-fat diet (HFD) feeding or hypoxic treatment.MethodsNAFLD model was induced in mice by HFD feeding, and in cultured primary hepatocytes by administration of palmitate acid. Mouse hypoxic model was produced by placing the mice in a Animal incubator with oxygen concentration at 75% followed by a 21% oxygen supplement. Hypoxic condition was mimicked by treating the hepatocytes with cobalt chloride (CoCl2) or 1% oxygen supply. Pimonidazole assay was conducted to evaluate hypoxia. Lipid metabolic genes were measured by real-time polymerase-chain reaction. HIF-1α and HIF-2α genes were silenced by siRNA.ResultsHFD feeding and palmitate acid treatment provoked severe hepatic hypoxia along with TG accumulation in mice and in cultured primary hepatocytes respectively. Conversely, hypoxia induced hepatic TG accumulation in mice and in cultured primary hepatocytes. Hypoxic treatment inhibited the expression of lipolytic genes, while increased the expression of lipogenicgenes in mice. Although both lipotoxicity and hypoxia could activate hepatic hypoxia-induced factor 1α and 2α, while neither lipotoxicity- nor hypoxia- induced hepatic steatosis was affected when HIF was knocked down.ConclusionsHFD resulted in hepatic TG accumulation and concomitant hypoxia. Conversely, hypoxia induced hepatic TG accumulation in mice and in cultured heptocytes. Thus lipotoxicity and hypoxia might work as reciprocal causation and orchestrate to promote the development of NAFLD.

Huangjinya Black Tea Alleviates Obesity and Insulin Resistance via Modulating Fecal Metabolome in High-Fat Diet-Fed Mice.

Huangjinya is a light-sensitive tea mutant containing low levels of tea polyphenols. Currently, most studies focused on characteristics formation, free amino acid metabolism and phytochemical purification. The biological activity of Huangjinya black tea (HJBT) on metabolic syndrome regarding fecal metabolome modulation is unavailable and is studied herein. High-fat diet (HFD)-fed mice are treated with HJBT for 9 weeks, various metabolic biomarkers and fecal metabolites are determined. HJBT reduces adipogenic and lipogenic gene expression, enhances lipolytic gene expression, decreases adipocyte expansion, and prevents the development of obesity. HJBT reduces lipogenic gene expression, increases fatty acid oxidation-related genes expression, which alleviates liver steatosis. HJBT enhances glucose/insulin tolerance, increases insulin/Akt signaling, attenuates hyperlipidemia and hyperglycemia, prevents the onset of insulin resistance. HJBT modulates bile acid metabolism, promotes secondary/primary bile acid ratio; increases short-chain fatty acids production, promotes saturated and polyunsaturated fatty acids content; reduces carnitines and phosphocholines, but increases myo-inositol content; decreases branched-chain and aromatic amino acids content; increases the metabolite content related to pentose phosphate pathway. This study reported the association between fecal metabolome modulation and metabolism improvement due to HJBT administration, proposes HJBT as a dietary intervention for preventing obesity and metabolic disorders.

Expression Profiling of Lipolytic and Long-Chain Fatty Acid Biosynthesis Genes in Catfish Larvae Fed With Graded Lipid Levels

This study was designed to investigate the effect of dietary lipid levels on the mRNA transcripts of lipid metabolic regulatory genes. Nine combinations of experimental diets containing graded lipid (80, 100 and 120 g/Kg) and protein (450, 500 and 550 g/Kg) levels were fed to the Clarias magur (Indian walking catfish) larvae from 14-35 dph (day post hatching). All the lipolytic genes such as lipoprotein lipase (LPL), pancreatic triacylglycerol lipase (PL) and bile salt-activated lipase (BAL) and genes for long chain poly unsaturated fatty acid (LC-PUFA) biosynthetic enzymes like fatty acyl desaturase-2 (FADS2), fatty acyl desaturase-5 (FADS5) and elongase (ELOV) were expressed in a wide range of tissues. High abundance of mRNA transcript levels of lipolytic genes was detected in intestine and liver, and similarly, desaturases and elongase were predominantly found to express in liver, brain and intestine. Among the diets a significantly high expression of both lipolytic and LC-PUFA biosynthetic genes were observed at 8% dietarylipid level. The expression of all the studied genes was down-regulated at 12% dietary lipid contents. Hence, the present study concludes that the efficient nutrient utilization and the lipid metabolic pathway occur at the optimum dietary lipid level of 8% in C. magur larvae.

The Effects of Triterpenoid Saponins from the Seeds of Momordica cochinchinensis on Adipocyte Differentiation and Mature Adipocyte Inflammation.

Obesity is a medical condition in which abnormal or excessive fat accumulates to an extent that is associated with various diseases. In our ongoing research to figure out natural products with anti-obesity effects, a phytochemical investigation of the EtOH extract of the seeds of Momordica cochinchinensis was carried out, which resulted in the isolation of two major triterpenoid saponins: gypsogenin 3-O-β-d-galactopyranosyl(1→2)-[α-l-rhamnopyranosyl (1→3)]-β-d-glucuronopyranoside (1) and quillaic acid 3-O-β-d-galactopyranosyl(1→2)-[α-l-rhamnopyranosyl(1→3)]-β-d-glucuronopyranoside (2). Then, the effects of the isolated triterpenoid saponins (1 and 2) on adipocyte differentiation were evaluated, and it was demonstrated that the isolated saponin (1) showed inhibitory effects on adipogenesis. In mature adipocytes, the isolated saponin (1) reversed tumor necrosis factor α (TNFα)-induced proinflammatory cytokine gene expression. Additionally, the isolated saponin (1) reduced lipolytic gene expression leading to decreased basal lipolysis activity. Collectively, these findings suggest that saponin (1) of M. cochinchinensis exerts beneficial effects in the regulation of adipogenesis and adipocyte inflammation and could be a potential therapeutic alternative in the treatment of obesity-induced metabolic diseases.

Taiwanese green propolis ethanol extract promotes adipocyte differentiation and alleviates TNF-α-mediated downregulation of adiponectin expression

Abstract The objective was to examine the effects of Taiwanese green propolis (TGP) ethanol extract on adipocyte differentiation and lipolysis. TGP ethanol extract significantly enhanced the differentiation of murine mesenchymal stem cells into adipocytes, and this was accompanied by an increase in intracellular triglyceride content and adiponectin levels. TGP ethanol extract significantly increased the expression of adipogenic transcription factor-associated genes in murine mesenchymal stem cells after hormonal induction of adipogenesis. TGP ethanol extract was able to alleviate norepinephrine-induced lipolysis in differentiated adipocytes, which was accompanied by a decrease in lipolytic gene expression. Besides, TGP ethanol extract could reduce the tumor necrosis factor-α (TNF-α)-mediated inhibition of adiponectin gene expression and secretion during adipogenic differentiation of mesenchymal stem cells and in differentiated adipocytes. These results demonstrate that TGP ethanol extract enhances adipocyte differentiation and is capable of reversing the inhibitory effects of TNF-α on adipocyte differentiation and adiponectin expression in differentiated adipocytes.

Adipose-specific inactivation of thyroid stimulating hormone receptors in mice modifies body weight, temperature and gene expression in adipocytes.

BackgroundIn obesity, the expression level of thyroid stimulating hormone receptor in adipose tissue is reduced and the levels of thyroid stimulating hormone (TSH) are often elevated within the normal range.Purpose/AimTo investigate the role of TSHR in brown and white adipose tissue (AT) using TSHR knockout (KO) mice and the physiological phenotypes affected by the TSHR knockout.MethodsAT‐specific TSHR KO male mice and wild type (WT) controls were given a high‐fat diet (HFD) or a control diet (CD). Body weights and food consumption were recorded for 20 weeks and body temperatures for the first 3 weeks. At termination, white and brown adipocytes were isolated. Gene expressios was investigated using real‐time PCR. In a subgroup of female KO mice, glucose tolerance was investigated.ResultsTSHR were partially knocked out in KO mice, which gained more weight than WT mice when fed both a CD (p = .03) and HFD (p = .003). Body temperatures were lower in KO mice on CD (p <.001) and on HFD (p <.001) than WT controls. This was in agreement with reduced gene expression of UCP1 in brown adipocytes in the KO mice. Glucose tolerance was significantly impaired in KO mice on CD mice before termination (p <.01). Expression of adipogenic and lipolytic genes were reduced in KO mice, which was exacerbated by HFD. The mRNA levels of adipokines including ADIPOQ and LEP were altered in white adipocytes of KO mice.ConclusionsTSHR KO led to dysfunction of both white and brown AT and predisposition to excess body weight gain in mice. Our data show that TSHR in AT regulates glucose tolerance, lipid metabolism, adipokine profile, and thermogenesis.

Dietary berberine regulates lipid metabolism in muscle and liver of black sea bream (Acanthopagrus schlegelii) fed normal or high-lipid diets.

The present study investigated the influence of berberine (BBR) supplementation in normal and high-lipid (HL) diets on lipid metabolism and accumulation in black sea bream (Acanthopagrus schlegelii). BBR was supplemented at 50 mg/kg to control (Con, 11·1 % crude lipid) and high-lipid (HL, 20·2 % crude lipid) diets and named as ConB and HLB, respectively. After the 8-week feeding trial, fish body length and specific growth rate were significantly reduced by HL diets (P < 0·05). Muscle and whole-body crude lipid contents were significantly influenced by both BBR supplementation and dietary lipid level. Fish fed the HLB diet had significantly lower serum TAG, LDL-cholesterol contents and alanine aminotransferase activity compared with the HL group. The HL group presented vast lipid accumulation in the liver, and hypertrophied hepatocytes along with large lipid droplets, and translocation of nuclear to the cell periphery. These abnormalities in black sea bream were alleviated in the HLB group. BBR supplementation in the HL diet significantly down-regulated the hepatic expression levels of acetyl-CoA carboxylase α, sterol regulatory element-binding protein-1, 6-phosphogluconate dehydrogenase, glucose 6-phosphate dehydrogenase and pparγ, whereas the lipoprotein lipase, hormone-sensitive lipase and carnitine palmitoyltransferase 1a expression levels were significantly up-regulated. However, the expression levels of these genes showed opposite trends in muscle (except for pparγ). In conclusion, dietary BBR supplementation in the HL diet reduced hepatic lipid accumulation by down-regulating lipogenesis gene expression and up-regulating lipolysis gene expression, and it increased muscle lipid contents with opposite trends of the mechanism observed in the liver.