Sterol Regulatory Binding Protein-1c Research Articles

Balancing act: How cholesterol and phospholipids influence juvenile mud crab Scylla paramamosain growth and lipid metabolism

A 2 × 3 two-factor experiment was designed to assess the effects of dietary cholesterol (CHO) and phospholipids (PLs) on growth and lipid metabolism in early juvenile mud crabs (0.01 g crab−1). The experimental diets were designed with two CHO levels: 0.40 % (LCH) and 0.80 % (HCH), and three PLs levels: 1.80 % (LPL), 2.50 % (MPL), and 3.20 % (HPL). The 58-day aquaculture trial demonstrated that the LCH-HPL group achieved the best growth performance in mud crabs, characterized by the highest final body weight, weight gain, and specific growth rate. Regarding whole-body composition, dietary PLs increased total cholesterol (T-CHO), PLs, triglyceride (TG), and crude lipid content in the LCH groups. Mud crabs in the HCH groups had a higher proportion of saturated fatty acids, a lower proportion of monounsaturated fatty acids, and increased gene expression of sterol regulatory element binding protein 1c (srebp-1c) and fatty acid synthase (fas) compared to those in the LCH groups. As the dietary PLs increased, mud crabs in the LCH groups exhibited up-regulation in the expression of genes, including srebp-1c, fas, elongation of very long-chain fatty acid protein 4 (elovl4), elovl6, and Δ9-fatty acid desaturase (Δ9-fad). In the HCH groups, elevated dietary PLs resulted in the down-regulation of fatty acid binding protein (fabp) gene expression. In addition, high levels of dietary CHO and PLs (HCH-HPL) inhibited the catalase activity of mud crabs, resulting in a significant increase in the malondialdehyde content. Correlation analysis revealed that dietary CHO was positively correlated with the expression of long-chain polyunsaturated fatty acids synthesizing genes, and dietary PLs were positively correlated with the whole-body lipid content of mud crabs. Additionally, a positive correlation was found between the growth performance and whole-body content of crude protein, crude lipid, and antioxidant capacity in mud crabs.

Regulation of hepatic lipogenesis by asymmetric arginine methylation

Background and aimsHepatic lipogenesis is elevated in nutrient abundant conditions to convert the excess carbohydrate into triacylglycerol (TAG). Fatty acyl moiety of TAG is eventually transported into adipose tissues by very low density lipoprotein, leading to the accumulation of TAG as a preferred storage form of excess energy. Disruption of the balance between TAG clearance and synthesis leads to the accumulation of lipids in the liver, leading to the progression of non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis. Protein arginine methyltransferase (PRMT) 6 has been linked to the various metabolic processes including hepatic gluconeogenesis, muscle atrophy and lipodystrophy in mouse models. However, the role of PRMT6 in the control of hepatic lipogenesis has not been elucidated to date. MethodsWe assessed the interaction between PRMT6 and LXR alpha by using co-immunoprecipitation assay. The specific arginine residue of LXR alpha that is methylated by PRMT6 was assessed by LC-MS/MS assay and the functional consequences of LXR alpha methylation was explored by mSREBP-1c luciferase assay. The effect of PRMT6 on hepatic lipogenesis was assessed by adenovirus-mediated ectopic expression of PRMT6 or knockdown of PRMT6 via shRNA in hepatocytes. Finally, the role of PRMT6 in hepatic lipid metabolism in vivo was explored by either ectopic expression of LXR alpha mutant that is defective in PRMT6-mediated arginine methylation or knockdown of PRMT6 in liver. ResultsWe found that promoter activity of sterol regulatory element binding protein (SREBP) 1c is robustly activated by PRMT6. Interestingly, we demonstrated that PRMT6 binds to LXR alpha, a transcription factor for SREBP-1c, via its LXXLL motif, leading to the asymmetric dimethylation of an arginine residue and activation of this protein. Indeed, ectopic expression of PRMT6 in hepatocytes led to the enhanced expression of LXR alpha target genes in the lipogenic pathway. Conversely, genetic or pharmacological inhibition of PRMT6 diminished expression of lipogenic genes and the lipid accumulation in primary hepatocytes. Mechanistically, we found that asymmetric dimethylation of LXR alpha led to the dissociation of small heterodimer partner (SHP), a transcriptional co-inhibitor of this factor, resulting in the activation of LXR alpha-mediated transcriptional process. Finally, we showed that disruption of asymmetric dimethylation of LXR alpha in the liver led to the diminished expression of genes in the lipogenesis, resulting in the reduced hepatic lipid accumulation in high fat diet-fed mice in vivo. ConclusionsWe showed that PRMT6 modulates LXR alpha activity by conferring asymmetric dimethylation of arginine 253, thus blocking SHP-mediated inhibition and promoting hepatic lipid accumulation. These results suggest that PRMT6 is critical in the control of lipid homeostasis by regulation of LXR alpha-mediated lipogenesis in the liver.

Taurine Activates SIRT1/AMPK/FOXO1 Signaling Pathways to Favorably Regulate Lipid Metabolism in C57BL6 Obese Mice.

The identification of novel therapeutic agents capable of modulating lipid metabolism holds a promising potential in combating obesity and its associated complications. This study is conducted to evaluate the lipid lowering effect of dietary taurine administration on high-fat fed C57BL6 mice and to study the mechanism by which taurine impacts lipid metabolism. C57BL6 mice are grouped into four (n = 6): i) normal diet (ND), ii) a high-fat diet (HFD), iii) HFD+orlistat (STD), iv) HFD + taurine (TAU) group for 12 weeks. The results show that taurine administration for 12 weeks reduces high fat-induced weight gain, and liver weight when compared with HFD fed mice. It also improves serum biochemical parameters like total cholesterol and triglycerides. Sirtuin 1 (SIRT1) activity, Nicotinamide adenine dinucleotide (NAD+) levels, SIRT1 mRNA, and protein expression are increased in HFD+TAU diet group as compared to HFD group. Taurine treatment suppresses the expression of lipogenic genes (sterol regulatory element binding protein 1c [SREBP1c], fatty acid synthase [FAS], Peroxisome proliferator-activated receptor gamma [PPARγ]) and increases the expression of β-oxidation (peroxisome proliferator-activated receptor alpha [PPARα], liver x receptor beta [LXRβ], peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC1α], AMP-activated protein kinase [AMPK]) and lipolytic (forkhead box protein O1 [FOXO1]) genes. Further, taurine mitigates hepatic inflammation by suppressing nuclear factor kappa B (NF-κB) gene expression and pro-inflammatory cytokine markers (IL-6, IL-1β, and TNFα). Taurine exerts lipid lowering effects through activating SIRT1/AMPK/FOXO1 signaling pathways and regulating their downstream targets.

Ilex paraguariensis A.St.-Hil. improves lipid metabolism in high-fat diet-fed obese rats and suppresses intracellular lipid accumulation in 3T3-L1 adipocytes via the AMPK-dependent and insulin signaling pathways.

Obesity is closely associated with several chronic diseases, and adipose tissue plays a major role in modulating energy metabolism. This study aimed to determine whether Mate, derived from I. paraguariensis A.St.-Hil., ameliorates lipid metabolism in 3T3-L1 adipocytes and high-fat diet (HFD)-fed obese Sprague-Dawley (SD) rats. 3T3-L1 adipocytes were cultured for 7 days, following which intracellular lipid accumulation and expression levels of lipid metabolism-related factors were examined. Dorsomorphin was used to investigate the potential pathways involved, particularly the adenosine monophosphate-activated protein kinase (AMPK)- dependent pathway. Mate was administered to rat HFD-fed obese SD models for 8 consecutive weeks. The expression of lipid metabolism-related factors in the organs and tissues collected from dissected SD rats was evaluated. Mate suppressed intracellular lipid accumulation in 3T3-L1 adipocytes, increased the protein and gene expression levels of AMPK, hormone sensitive lipase (HSL), calmodulin kinase kinase (CaMKK), liver kinase B1 (LKB1), protein kinase A (PKA), CCAAT/enhancer binding protein β (C/EBPβ), insulin receptor b (IRβ), and insulin receptor substrate 1 (IRS1) (Tyr465), and decreased those of sterol regulatory element binding protein 1C (Srebp1c), fatty acid synthase (FAS), peroxisome-activated receptor γ (PPARγ), and IRS1 (Ser1101). Furthermore, an AMPK inhibitor abolished the effects exerted by Mate on intracellular lipid accumulation and HSL and FAS expression levels. Mate treatment suppressed body weight gain and improved serum cholesterol levels in HFD-fed obese SD rats. Treatment with Mate increased the protein and gene expression levels of AMPK, PKA, Erk1/Erk2 (p44/p42), and uncoupling protein 1 and reduced those of mammalian target of rapamycin, S6 kinase, Srebp1c, ap2, FAS, Il6, Adiponectin, Leptin, and Fabp4 in rat HFD-fed obese SD models. Mate suppressed intracellular lipid accumulation in 3T3-L1 adipocytes and improved lipid metabolism in the epididymal adipose tissue of HFD-fed obese SD rats via the activation of AMPK-dependent and insulin signaling pathways.

Modulation of lipid metabolism by oyster peptides in mice with high-fat diet-induced obesity

Oysters (Crassostrea gigas) are rich in proteins and a source of valuable peptides. Previous studies have revealed that oral administration of oyster peptides (OP) obtained by simulating gastrointestinal digestion reduced the weight of mice. However, the underlying regulatory mechanisms are unclear. We speculate that OP may be able to reduce fatty acid absorption by inhibiting pancreatic lipase activity. Therefore, we investigated the regulatory effects of OP on lipid metabolism in mice with high-fat diet-induced obesity. The body weight (BW), fat weight, lipid parameters, lipid metabolism-related gene expression, and serum lipid profiles were determined by MS-based lipidomics. Daily supplementation with 500 mg of OP/kg BW in obese mice reduced their BW gain and organ weights, improved dyslipidemia, and downregulated the genes expression of encoding proteins involved in fatty acid uptake, including acetyl coenzyme A carboxylase 1 (Acc1), fatty acid synthase (Fas), and sterol regulatory element binding protein 1c (Srebp-1c). Moreover, administration of OP resulted in significant changes in the lipid profile of mice. We screened 129 differential metabolites to identify biomarkers for OP intervention and analyzed the effects of OP on the metabolism of sphingolipids, glycerophospholipids, linoleic acid, and α-linolenic acid. In summary, OP can improve obesity-induced lipid metabolism dysfunctions by inhibiting enzyme activity and regulating fatty acid uptake.

The role of vitamin D3 in modulating the interplay between NLRP3 inflammasome and autophagy in NASH

Damage-associated molecular patterns released upon hepatocyte injury ensuing non-alcoholic steatohepatitis (NASH) can stimulate innate immunity by activating NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, thereby triggering pro-inflammatory cascades in the liver. Aberrant NLRP3 activation allied to compromised autophagic clearance of its components contributes to the progression of multiple inflammatory diseases. Such intricate interplay, however, was not fully deciphered in NASH. Prior studies have illuminated the ability of vitamin D3 to temper inflammasome activation in several contexts, prompting us to probe the impact of vitamin D3, particularly its active form, calcitriol (CAL), on NLRP3 overactivation in a high-fat diet (HFD)-based NASH model and its potential dependence on autophagy. Hydroxychloroquine (HCQ), an autophagy inhibitor, was co-administered with CAL to examine the likely modulation of the NLRP3/autophagy crosstalk. Our results showed that treatment with CAL countervailed the histopathological derangement reported in the livers of HFD-fed mice that paralleled a restoration of vitamin D receptor gene expression and reduction in sterol regulatory element binding protein 1c levels. Moreover, p62 was curtailed with CAL treatment indicating autophagy induction. CAL also prompted a reduction in NLRP3, caspase-1, gasdermin D, and IL-18 protein levels along with the apoptosis-associated speck-like protein (ASC) gene expression. Treatment with CAL also reduced IL-1β and caspase-3 immunoreactivities compared to control. Intriguingly, CAL modulatory effects on inflammasome activation were curbed in the group that received HCQ, suggesting a potential autophagy dependency. Accordingly, the current study suggests that CAL was capable of ameliorating NASH via inhibiting NLRP3 inflammasome activation in an autophagy-dependent manner.

MiR-871-5p / PGC1α regulates aging-induced lipid deposition in hepatocytes through fatty acid β-oxidation.

This study investigated the role of the miR-871-5p/proliferator-activated receptor α (PGC1α) pathway in ameliorating hepatic steatosis. We examined miR-871-5p expression in liver tissues of ageing mice and AML12 senescent cells co-induced by low serum and palmitic acid (PA). Bioinformatics and multiple experiments were employed to validate the expression level of the target gene PGC1α for miR-871-5p. In this study, we aimed to investigate the potential role of miR-871-5p in regulating hepatic lipid deposition associated with ageing. To do so, we performed in vitro transfection of both miR-871-5p mimic and inhibitor into senescent hepatocytes. Our results showed that miR-871-5p could inhibit PGC1α expression and cause lipid deposition in the liver due to ageing. MiR-871-5p controls this process by regulating PGC1α / fatty acid β oxidation. H&E staining displayed the appearance of fat vacuoles in the livers of ageing mice, and fatty acid β oxidation-related genes (acyl-coenzyme A oxidase 1 carnitine palmitoyl transferase 1α (ACOX1), and peroxisome proliferator-activated receptor α (PPARα)) expression was significantly reduced. Lipogenic genes (sterol regulatory element binding protein 1C (SREBP-1C), fatty acid synthase (FASN)) expression level was increased in the livers of ageing mice. In AML12 cells co-induced by low serum and PA, miR-871-5p mimics decreased PGC1α expression and increased lipid droplet accumulation in senescent hepatocytes. Conversely, miR-871-5p inhibitor promoted PGC1α expression and reduced lipid deposition in senescent hepatocytes. Our findings suggest that inhibiting miR-871-5p could be crucial in ameliorating aging-associated hepatic steatosis. These findings offer valuable insights into the molecular mechanisms driving hepatic steatosis in ageing.

Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice

Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice

Pheophorbide A isolated from Gelidium amansii inhibits adipogenesis by regulating adipogenic transcription factors and AMPK in 3T3-L1 adipocytes

Adipocyte lipid accumulation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. As part of our efforts to isolate antiobesity agents from natural products, we first isolated the active compound from the extract of Gelidium amansii through bioassay-guided fractionation. We then hypothesized that pheophorbide A isolated from G amansii inhibits adipogenesis by downregulating adipogenic transcription factors; therefore, the antiadipogenic effects of pheophorbide A were investigated in 3T3-L1 adipocytes. On differentiation of 3T3-L1 preadipocytes into adipocytes, they were treated with pheophorbide A (0-83 µM). Pheophorbide A inhibited triglyceride accumulation (half maximal inhibitory concentration = 114.2 µM) and stimulated glycerol release in a dose-dependent manner in 3T3-L1 adipocytes. In addition, pheophorbide A significantly decreased leptin concentrations in 3T3-L1 adipocytes. Pheophorbide A inhibited adipogenesis by suppressing the expression of adipogenic transcriptional factors including peroxisome proliferator-activated receptor γ, CCATT/enhancer binding protein α, sterol regulatory element binding protein 1c, and fatty acid synthase. It also induced the expression of phosphorylation of AMP-activated protein kinase. Therefore, these results suggest that pheophorbide A may be useful for preventing or treating obesity because of its inhibitory effect on adipogenesis.

Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism.

BackgroundGlobally, obesity is a significant public problem, especially when aging. Sesamol, a phenolic lignan present in sesame seeds, might have a positive effect on high-fat diet (HFD)-induced obesity associated with aging.ObjectiveThe purpose of current research study was to explore salutary effects and mechanisms of sesamol in treating alimentary obesity and associated metabolic syndrome in middle-aged mice.MethodsC57BL/6J mice aged 4–6 weeks and 6–8 months were assigned to the young normal diet group, middle-aged normal diet group, middle-aged HFD group, and middle-aged HFD + sesamol group. At the end of experiment, glucose tolerance test and insulin tolerance test were performed; the levels of lipids and oxidative stress-related factors in the serum and skeletal muscle were detected using chemistry reagent kits; lipid accumulation in skeletal muscle was observed by oil red O staining; the expressions of muscular glucose and lipid metabolism associated proteins were measured by Western blotting.ResultsSesamol decreased the body weight and alleviated obesity-associated metabolism syndrome in middle-aged mice, such as glucose intolerance, insulin resistance, dyslipidemia, and oxidative stress. Moreover, muscular metabolic disorders were attenuated after treatment with sesamol. It increased the expression of glucose transporter type-4 and down-regulated the protein levels of pyruvate dehydrogenase kinase isozyme 4, implying the increase of glucose uptake and oxidation. Meanwhile, sesamol decreased the expression of sterol regulatory element binding protein 1c and up-regulated the phosphorylation of hormone-sensitive lipase and the level of carnitine palmityl transferase 1α, which led to the declined lipogenesis and the increased lipolysis and lipid oxidation. In addition, the SIRT1/AMPK signaling pathway was triggered by sesamol, from which it is understood how sesamol enhances glucose and lipid metabolism.ConclusionsSesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism, which might be associated with the stimulation of the SIRT1/AMPK pathway.

Gut microbiota modulation in Alzheimer's disease: Focus on lipid metabolism

Alzheimer's disease (AD) and age-related dementias represent a major and increasing global health challenge. Unhealthy diet and lifestyle can unbalance the intestinal microbiota composition and, consequently energy metabolism, contributing to AD pathogenesis. Impairment of cerebral cholesterol metabolism occurs in both aging and AD, and lipid-lowering agents have been associated to a lower risk of neurodegenerative diseases, but the link between blood lipid profile and AD remains a matter of debate. Recently, probiotics have emerged as a promising and safe strategy to manipulate gut microbiota composition and increase the host health status through a multi-level mechanism that is currently under investigation. Specifically, oral supplementation with a multi-strain probiotic formulation (SLAB51) reduced amyloid beta aggregates and brain damages in a triple transgenic mouse model of AD (3xTg-AD). Treated mice showed improved cognitive functions in response to an enrichment of gut anti-inflammatory metabolites, increased plasma concentrations of neuroprotective gut hormones, and ameliorated glucose uptake and metabolism. This work focuses on the evaluation of the effects of SLAB51 chronic administration on lipid metabolism in 3xTg-AD mice and the respective wild-type counterpart. On this purpose, 8 weeks old mice were orally administered with SLAB51 for 4 and 12 months to analyze the plasma lipid profile (using lipidomic analyses and enzymatic colorimetric assays), along with the cerebral and hepatic expression levels of key regulators of cholesterol metabolism (through Western blotting and ELISA). Upon probiotics administration, cholesterol biosynthesis was inhibited in AD mice with a process involving sterol regulatory element binding protein 1c and liver X receptors mediated pathways. Decreased plasma and brain concentration of 27-hydroxycholesterol and increased brain expression of cholesterol 24S-hydroxylase indicated that alternative pathways of bile acid synthesis are influenced. The plasmatic increase of arachidonic acid in treated AD mice reflects dynamic interactions among several actors of a complex inflammatory response, in which polyunsaturated fatty acids can compete each other and simultaneously co-operate in the resolution of inflammation. These evidence, together with the hypocholesterolemic effects, the ameliorated fatty acids profile and the decreased omega 6/omega 3 ratio successfully demonstrated that microbiota modulation through probiotics can positively change lipid composition in AD mice, with arachidonic acid representing one important hub metabolite in the interactions among probiotic-induced lipid profile changes, insulin sensitivity, and inflammation.

An In Vitro Study on the Effects of Aromatic Hydrocarbons 1- Naphthol and Dibenz[a,h]anthracene in HepG2 Cells

Liver cells (HepG2) were treated with well known toxic aromatic hydrocarbons 1-Naphthol and Dibenz[a,h]anthracene. Naphthol at 20-40µg/ml affected significant increase in the levels of reactive oxygen species in the cells.. Reactive nitrogen intermediates increased to an extent of 2.4 to 3.8 fold in cells treated with naphthol over a range of 20-80 µg/ml. Expression of antioxidant enzyme Glutathione peroxidase was found to increase two fold, while catalase expression was found to decrease by 21% on exposure to 1-Naphthol. Dibenz[a,h]anthracene did not affect discernible changes in the expression of these enzymes Induction of CYP1A1 mRNA by Naphthol at 60µg/ml was around 45 fold higher than untreated cells. Dibenz anthracene at a dose of 5µg/ml was found to be a potent inducer of CYP1A1 as it elevated expression of CYP1A1 mRNA to an extent of 350 fold. . Naphthol exhibited lipogenic potential in HepG2 cells. Concommitant increase in Sterol regulatory element binding protein 1c was observed.

The Cordyceps militaris-Derived Polysaccharide CM1 Alleviates Atherosclerosis in LDLR(-/-) Mice by Improving Hyperlipidemia.

Atherosclerotic cardiovascular disease has a high mortality worldwide. Our lab previously purified a polysaccharide designated as CM1 with (1→4)-β-D-Glcp and (1→2)-α-D-Manp glycosyls as the backbone. In this study, we investigated the anti-atherosclerosis effect of CM1 and the underlying mechanisms of action in a low-density lipoprotein receptor knockout (LDLR(-/-) mouse model. It was found that CM1 significantly decreased the formation of atherosclerotic plaques. Mechanistically, CM1 enhanced plasma level of apolipoprotein A-I and decreased the plasma levels of triglyceride, apolipoprotein B, and total cholesterol. In the absence of LDLR, CM1 elevated the expression of very low-density lipoprotein receptor for liver uptake of plasma apolipoprotein B-containing particles and reduced hepatic triglyceride synthesis by inhibiting sterol regulatory element binding protein 1c. CM1 improved lipids excretion by increasing the liver X receptor α/ATP-binding cassette G5 pathway in small intestine. CM1 reduced lipogenesis and lipolysis by inhibiting peroxisome proliferator-activated receptor γ and adipose triglyceride lipase in epididymal fat. Furthermore, CM1 improved lipid profile in C57BL/6J mice. Collectively, CM1 can modulate lipid metabolism by multiple pathways, contributing to reduced plasma lipid level and formation of atherosclerotic plaques in LDLR(−/−) mice. This molecule could be explored as a potential compound for prevention and treatment of hyperlipidemia and atherosclerosis.

Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats

BackgroundBoth fructose consumption and chronic stress contribute to the development of metabolic disorders. The consequences of such combination are not fully understood. ObjectiveWe investigated whether fructose supplementation and chronic stress synergistically disturb hepatic lipid and glucose metabolism. The role of energy sensing, redox, and inflammatory status during development of metabolic disturbances was investigated. MethodsFemale Wistar rats, aged 2.5 mo, were divided into 4 experimental groups: control (C) fed a standard diet (commercial food and drinking water); fructose (F) fed the same food and 10% fructose solution; stress (S) fed the standard diet and subjected to chronic unpredictable stress and, stress + fructose (SF) combining conditions F and S as above. Stress included daily stressors: cold water forced swimming, physical restraint, cold room, wet bedding, rocking, switching, or tilting cages. After 9 wk, hepatic enzymes and transcription factors involved in gluconeogenesis, lipogenesis, fatty acid oxidation, antioxidative defence, energy sensing, and cytokines were assessed by qPCR, Western blotting, and spectrophotometry and analyzed by 2-factor ANOVA. ResultsFructose increased AMP-activated protein kinase (AMPK) phosphorylation (40%; P < 0.05) and the ratio of inhibitory phosphorylation to total acetyl-CoA carboxylase (46%; P < 0.01), and decreased sterol regulatory element binding protein 1c nuclear translocation by 30% (P < 0.05) in F and SF compared with C rats. Increased phosPck (phoenolpyruvate carboxykinase) (85%) and G6pase(glucose-6-phosphatase) (55%) was observed in S rats (P < 0.05). A 40% decrease in Apob (apolipoprotein B-100) and an increase in hepatic lipids (P < 0.05), together with a double increase in TNF-α (P < 0.001), were observed in S rats, but without liver histopathological changes. These stress effects on lipid accumulation and TNF-α were abolished in SF rats (P < 0.05). ConclusionsFructose does not enhance stress effects on hepatic lipid and glucose metabolism but attenuates its effects on hepatic lipid accumulation and inflammation, suggesting that, in female rats, AMPK activation prevails over stress-induced effects.

Garlic Scape (Allium sativum L.) Extract Decreases Adipogenesis by Activating AMK-Activated Protein Kinase During the Differentiation in 3T3-L1 Adipocytes.

Regulating adipogenesis and lipogenesis in white adipose tissue (WAT) is an efficient strategy to reduce obesity. This study investigates whether garlic scape extract (GSE) has anti-adipogenic and anti-lipogenic effects and which stage of adipogenesis is critical for its effect using 3T3-L1 cells. 3T3-L1 cells that were treated with GSE during adipogenesis and differentiation exhibited reduced peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein a (Cebpa) and Cebpb, acetyl-CoA carboxylase, fatty acid synthase, sterol regulatory element binding protein 1c, diacylglycerol acyltransferase 1, and perilipin 1 genes. When the cells were treated with GSE during postdifferentiation or during preadipocytes, they showed less reduction and no change, respectively. Consistent with this, lipid accumulation was strongly reduced in the cells that were treated during adipogenesis and differentiation and to a lesser extent in the cells that were treated during preadipocytes and postdifferentiation. Phosphorylation on AMP-activated protein kinase (AMPK) and its downstream proteins was increased together with increased carnitine palmitoyl transferase 1α and phosphorylation on hormone-sensitive lipase in the cells that were treated with GSE during differentiation. In summary, GSE reduced intracellular lipid accumulation by suppressing adipogenic and lipogenic genes and proteins by possibly the activation of AMPK signaling pathway during adipocyte differentiation. This result indicates that garlic scape may have the potential to prevent obesity by regulating lipid metabolism in WAT.

Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator’s, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1β secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway.

Gycyrrhizic acid alleviates atherosclerotic lesions in rats with diabetes mellitus.

Gycyrrhizic acid (GA), an inhibitor of high mobility group box 1 (HMGB1), inhibits inflammatory responses and is involved in the occurrence and development of several inflammation-related diseases. However, the role of GA in the atherosclerotic lesions caused by diabetes mellitus (DM) remains unknown. In the present study, Sprague Dawley rats were selected to desi=gn a diabetic atherosclerosis (AS) model. Rats from the DM-AS group were subsequently divided into DM-AS, DM-AS + GA (50 mg/kg) and DM-AS + GA (150 mg/kg) groups. Biochemical analyzers were used to measure levels of blood glucose, fasting insulin, total cholesterol, total triglyceride, low-density lipoprotein and high-density lipoprotein. The number of plaques was recorded after collection of thoracic aortas from the rats. The intimal thickness of arterial tissue was detected by hematoxylin and eosin staining. The expression levels of CD68 and α-smooth muscle actin (α-SMA) were detected by immunohistochemistry. The expression of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β in the serum of the rats was detected by ELISA. The expression of fatty acid synthetase, sterol regulatory element binding protein 1C, HMGB1 and receptor for advanced glycation end products (RAGE) was detected by western blotting. Reverse transcription quantitative PCR was used to detect the mRNA expression of HMGB1 and RAGE. The results demonstrated that GA treatment could decrease the body weight, blood glucose level and biochemical parameters of AS DM rats in a dose-dependent manner. In addition, GA decreased the intimal thickness of carotid artery and the formation of plaque in rats with diabetic AS. Furthermore, GA inhibited macrophage activation and decreased α-SMA expression in vascular smooth muscle cells, and decreased the expression of proteins (FAS and SREBP-1c) and inflammatory factors. Taken together, the findings from the present study demonstrated that GA may have a therapeutic effect on DM-associated AS. This study provides a theoretical basis for the treatment of diabetic AS.

Enhanced Inhibition of Adipogenesis by Chrysin via Modification in Redox Balance, Lipogenesis, and Transcription Factors in 3T3-L1 Adipocytes in Comparison with Hesperidin

Objective The present study was conducted to elucidate the in-vitro anti-oxidant and anti-adipogenic effect of the flavone, chrysin in comparison with the citrus bioflavonoid, hesperidin during adipogenic differentiation in 3T3-L1 mouse preadipocytes. Methods The effect of chrysin and hesperidin on adipogenic differentiation was evaluated using Oil red-O staining, triglyceride estimation, free glycerol release, and ROS accumulation. The expression of adipogenesis-related genes was evaluated in real time-polymerase chain reaction. Results 50 µmol chrysin or hesperidin did not affect the cell viability of 3T3-L1 preadipocytes and adipocytes, but significantly reduced preadipocyte clonal population, accumulation of intracellular lipid and ROS and consequently increased lipolysis and antioxidant enzyme defence. It also decreased the expression of major adipogenic transcription factors, CCAAT/enhancer-binding protein-β, peroxisome proliferator activated receptor-γ, sterol regulatory element binding protein 1c, fatty acid synthase and hormone sensitive lipase. Conclusion(s) Herein we have indicated, for the first time, the effective anti-adipogenic mechanism of chrysin by down-regulating adipogenesis, lipogenesis and ROS and up-regulating lipolysis and antioxidant enzyme in differentiated 3T3-L1 adipocytes. As a nutritional bioflavonoid, chrysin with its more effective inhibition on adipogenesis than hesperidin has the potential to be developed as an anti-adipogenic nutraceutical agent.

Mentha cordifolia Leaf Extract Improves Hepatic Glucose and Lipid Metabolism in Obese Mice Fed with High-Fat Diet.

Mentha cordifolia (MC) is a popular herb used to flavor food in Thailand that exhibits several biological effects. The present study aimed to determine the role of MC in regulating glucose and lipid metabolism in mice fed a high-fat diet (HFD). ICR obese mice were fed an HFD (45 kcal% lard fat) for 12 weeks, with MC (100 and 200 mg/kg/d) treatment from Week 7. After treatment with MC for 6 weeks, mice showed significantly lower rates of hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increased amounts of serum adiponectin. Furthermore, in mice treated with MC, serum interleukin-6 and tumor necrosis factor alpha were significantly inhibited and liver histology results showed decreased lipid accumulation and liver triglyceride content vs. untreated mice. In addition, MC treatment was associated with smaller fat cells and lower gene expression of liver sterol regulatory element binding protein 1c, acetyl-CoA carboxylase, and fatty acid synthase. However, MC treatment was associated with higher carnitine palmitoyltransferase 1a gene expression and significantly higher rates of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in liver, but lower levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. These results indicate MC regulates glucose and lipid metabolism in a HFD-induced obese mouse model, possibly via activation of AMPK signaling pathway.

The effects of quercetin on the expression of SREBP-1c mRNA in high-fat diet-induced NAFLD in mice.

The study aimed to determine the effect of quercetin on the expression of primary regulator gene involved in lipogenesis and triglycerides synthesis in the liver, and the sterol regulatory binding protein-1c (SREBP-1c) mRNA in non-alcoholic fatty liver disease (NAFLD) with a high-fat diet (HFD) model. Fifty-six Balb/c mice were divided into seven groups: standard feed; HFD; HFD and quercetin 50mg/kg for 28days; HFD and quercetin 100mg/kgBW for 28days; HFD and quercetin 50mg/kg for 14days; HFD and quercetin 100mg/kg for 14days; HFD and repaired fed for 14days. Quercetin was administered intraperitoneally. The animals were sacrificed 24h after the last treatment; the liver was taken for macroscopic, histopathological staining using hematoxylin-eosin and reverse transcription-PCR analysis sample. HFD significantly increased the expression of SREBP-1c mRNA; meanwhile, quercetin and repaired feedsignificantly reduced the expression of SREBP-1c mRNA in the liver. Quercetin at a dose of 50mg/kg and 100mg/kg also improved liver cells' pathological profile in high-fat diet NAFLD. The present study suggests that quercetin has an inhibitory effect on SREBP-1c expression and improved liver pathology in NAFLD mice.