Adipogenesis In Adipose Tissue Research Articles

PSIII-20 Transcriptional and Functional Analyses of Intramuscular, Subcutaneous, and Visceral Adipose Tissue in Finished Beef Cattle

Abstract Intramuscular adipose tissue (IMAT; marbling) deposition is a highly desired trait in beef cattle. Unlike excessive subcutaneous (SCAT) and visceral (VIAT) adipose tissue, which have relatively low value, increased marbling is associated with meat sensory traits and is a primary factor influencing beef quality grading in the U.S. However, this trait is difficult to achieve. Our objective was to assess depot-specific characteristics and gene profile of IMAT, SCAT, and VIAT in beef cattle. IMAT and SCAT samples from the longissimus muscle (9-11th ribs), and VIAT from the greater omentum were collected from four beef animals at harvest. Adipose tissue (AT) samples were flash frozen in liquid nitrogen, followed by RNA extraction (Trizol reagent) and RNA sequencing analysis on an Illumina Novaseq 6000 platform to generate 150 bp paired-end reads. DESeq2 R package was used for differential gene expression analysis (DEG) and DEG (P ≤ 0.05, log2FC ≥ 1) were evaluated for KEGG enrichment pathways. Remainder tissue samples were assessed for viscoelasticity (rheometer), collagen fibrillogenesis (kinetics), and adipocyte size (K2 Cellometer). Transcriptome analysis revealed over 4,000 DEG between IMAT and SCAT, over 3,000 DEG between VIAT and IMAT, and 1,018 DEG between VIAT and SCAT, thus indicating substantial transcriptional diversity among AT depots (Figure 1). Top upregulated genes in SCAT vs. IMAT were associated with increased lipid accumulation and regulation such as LIPE, LEP, ADIPOQ, PPARG, and extracellular matrix (ECM) remodeling, including collagens, MMP14, and TIMP4. Accordingly, enrichment analysis revealed an activation of PPARG signaling pathways and fatty acid metabolism in SCAT vs. IMAT, which are key for lipogenesis and adipogenesis (Figure 2). IMAT showed activation of pathways for thermogenesis and oxidative phosphorylation compared with both SCAT and VIAT, indicating that IMAT utilization may be more directed towards muscle function and development (Figure 2 and 3). Top VIAT DEG were primarily associated with immune cell adhesion, and immune response (CDHR1, TENM2, and TNFRSF9), suggesting a pro-inflammatory profile of visceral adiposity. Notably, enrichment analysis showed an activation of the immune function in VIAT compared with IMAT and SCAT (Figures 3 and 4). In agreement with transcriptome analysis, adipocyte size was increased in SCAT vs. IMAT and VIAT, implying higher lipid accumulation (Figure 5). SCAT was also stiffer and had increased collagen fibrillogenesis compared with IMAT, suggesting a key role for ECM in mechanisms of AT adipogenesis and lipogenesis (Figure 5). In summary, these results indicate that AT anatomical location impacts AT transcriptome, which may translate into functional differences in adipogenesis and ECM remodeling. Understanding transcriptional and functional differences among IMAT, SCAT and VIAT can help on the identification of target genes to modulate AT deposition in distinct areas of the body, therefore, improving quality of beef carcasses and industry profitability.

Lysozyme Gene Expression in 3T3-L1 Cells Sustains Expression of Adipogenic Genes and Adipocyte Differentiation.

Substantial levels of lysozyme in adipose tissue in association to obesity have been recently demonstrated in mice and humans. In addition, experiments in mice suggest that lysozyme might impact on adipose tissue adipogenesis. To further investigate the relationship between lysozyme and adipogenesis, in the present study, we aimed to study lysozyme (Lyz2) during 3T3-L1 adipocyte differentiation and its possible role in adipogenesis. Time course experiment during 3T3-L1 adipocyte differentiation indicated that Lyz2 gene expression decreased at day 4, which was caused by isobutylmethylxanthine administration, and recovered at the end of the process (day 8). Importantly, the impact of isobutylmethylxanthine-induced downregulation of Lyz2 gene expression on adipogenesis was not comparable to that observed in the full cocktail, questioning whether the reduction in lysozyme at early stage of adipocyte differentiation is relevant to this process. In fact, the depletion in Lyz2 expression had a negative impact on adipogenesis, and rosiglitazone administration failed to compensate for the anti-adipogenic effect observed in Lyz2 gene knockdown cells. Otherwise, when Lyz2 gene knockdown cells were co-cultured with control cells, these cells had higher expression of adipogenic genes than those co-cultured with themselves at the end of adipocyte differentiation. In conclusion, this study suggests that lysozyme expression in 3T3-L1 cells sustains expression of adipogenic genes and adipocyte differentiation.

TCDD-inducible Poly (ADP-ribose) Polymerase Promotes Adipogenesis of Both Brown and White Preadipocytes.

TCDD-inducible poly (ADP-ribose) polymerase (TiPARP) is a DNA repair enzyme with functions in energy metabolism, signal transduction, cell differentiation, and other biological processes, which may closely related to lipid metabolism and is highly expressed in adipose tissue. Adipose tissue can be divided into white adipose tissue (WAT) that stores energy and brown adipose tissue (BAT) that releases energy and generates heat. In the present study, we investigated whether TiPARP can affect adipogenesis in adipose tissue and thus participate in the development of obesity. BAT primary cells or 3T3-L1 cells infected with adenovirus expressing TiPARP or TiPARP-targeted short hairpin RNA (shTiPARP) were cultured to induce adipogenic differentiation. The expression of TiPARP was detected by real-time PCR and Western blotting. The expression of specific BAT- and WAT-related markers was detected by real-time PCR. The accumulation of lipid droplets in differentiated cells was detected by Oil Red O staining. TiPARP was highly expressed in both subcutaneous WAT and BAT, and TiPARP mRNA level increased significantly along with adipogenic differentiation. Activation of TiPARP or overexpression of TiPARP upregulated BAT-related markers in primary BAT cells and WAT-related markers in 3T3-L1 cells, together with increased lipid accumulation. On the contrary, knockdown of TiPARP downregulated expression of specific markers in both BAT primary cells and 3T3-L1 cells, together with decreased lipid accumulation. TiPARP regulates adipogenesis in both BAT primary cells and 3T3-L1 cells and therefore plays an important role in modulating maturity and lipid accumulation in brown and white adipocytes. These findings provide us with a new strategy for combating obesity.

An in-silico study to investigate the role of β-cryptoxanthin on obesity

Obesity is one of the significant risk factors commonly associated with lots of metabolic diseases penetrating in the younger age group population. In this study, we aimed to check the effectiveness of a carotenoid, β-cryptoxanthin, for reducing the adverse effect of obesity. The possible metabolic pathway of β-cryptoxanthin towards lowering obesity was hypothesized. Docking on different proteins involved in that pathway showed better binding affinity of β-cryptoxanthin with interactive proteins compared to the control. Stable and very strong binding of β-cryptoxanthin with PPAR-γ, PPAR-β/δ, and RAR-γ infer its effectiveness towards suppressing adipogenesis in Adipose tissue than other tissues. Furthermore, docking of β-cryptoxanthin with RAR showed better affinity than anti-obesity drugs for RAR induced adipogenesis suppression. Therefore, β-cryptoxanthin could be used as a potential natural ligand to treat obesity.

Homeostatic and pathogenic roles of the GM3 ganglioside.

Two decades ago, we achieved molecular cloning of ganglioside GM3 synthase (GM3S; ST3GAL5), the enzyme responsible for initiating biosynthesis of complex gangliosides. The efforts of our research group since then have been focused on clarifying the physiological and pathological roles of gangliosides, particularly GM3. This review summarizes our long-term studies on the roles of GM3 in insulin resistance and adipogenesis in adipose tissues, cholesterol uptake in intestine, and leptin resistance in hypothalamus. We hypothesized that GM3 plays a role in innate immune function of macrophages and demonstrated that molecular species of GM3 with differing acyl-chain structures and modifications functioned as pro- and anti-inflammatory endogenous Toll-like receptor 4 (TLR4) modulators in macrophages. Very-long-chain and α-hydroxy GM3 species enhanced TLR4 activation, whereas long-chain and unsaturated GM3 species counteracted this effect. Lipidomic analyses of serum and adipose tissues revealed that imbalances between such pro- and anti-inflammatory GM3 species promoted progression of metabolic disorders. GM3 thus functions as a physiological regulatory factor controlling the balance between homeostatic and pathological states. Ongoing studies based on these findings will clarify the mechanisms underlying ganglioside-dependent control of energy homeostasis and innate immune responses.

The role of transcription factor 7-like 2 in metabolic disorders.

Transcription factor 7-like 2 (TCF7L2), a member of the T cell factor/lymphoid enhancer factor family, generally forms a complex with β-catenin to regulate the downstream target genes as an effector of the canonical Wnt signalling pathway. TCF7L2 plays a vital role in various biological processes and functions in many organs and tissues, including the liver, islet and adipose tissues. Further, TCF7L2 down-regulates hepatic gluconeogenesis and promotes lipid accumulation. In islets, TCF7L2 not only affects the insulin secretion of the β-cells but also has an impact on other cells. In addition, TCF7L2 influences adipogenesis in adipose tissues. Thus, an out-of-control TCF7L2 expression can result in metabolic disorders. The TCF7L2 gene is composed of 17 exons, generating 13 different transcripts, and has many single-nucleotide polymorphisms (SNPs). The discovery that these SNPs have an impact on the risk of type 2 diabetes (T2D) has attracted thorough investigations in the study of TCF7L2. Apart from T2D, TCF7L2 SNPs are also associated with type 1, posttransplant and other types of diabetes. Furthermore, TCF7L2 variants affect the progression of other disorders, such as obesity, cancers, metabolic syndrome and heart diseases. Finally, the interaction between TCF7L2 variants and diet also needs to be investigated.

Adipose depot-specific effects of 16weeks of pioglitazone on in vivo adipogenesis in women with obesity: a randomised controlled trial.

In vitro and rodent studies suggest that pioglitazone, a thiazolidinedione, can promote adipogenesis in adipose tissue (AT); however, there is a lack of in vivo studies in humans to support these findings. The objectives of this randomised, placebo-controlled, parallel-arm trial were to test if pioglitazone stimulates in vivo adipogenesis in the subcutaneous adipose tissue depots and if these measures were related to metabolic health outcomes in women with obesity. Forty-one healthy women with obesity (20 black; 21 white; 29 ± 6years; BMI 32.0 ± 1.7kg/m2; 44.0 ± 3.6% body fat) were randomised to consume 30mg/day of pioglitazone (n = 21) or placebo (n = 20) for 16weeks. SAS v9.4 was used to generate the block randomisation code sequence (stored in password-protected files) with a 1:1 allocation ratio. The participants and study staff involved in assessing and analysing data outcomes were blinded to the group assignments. The trial was conducted at Pennington Biomedical Research Center and ended in 2016. At baseline and post-intervention, subcutaneous abdominal (scABD) and femoral (scFEM) AT biopsies were collected, and in vivo cellular kinetics (primary endpoint of the trial) were assessed by an 8week labelling protocol of deuterium (2H) into the DNA of adipose cells. Body composition was measured by dual-energy x-ray absorptiometry (DXA), scABD and visceral AT (VAT) by MRI, ectopic fat by 1H-MRS, and insulin sensitivity by an OGTT. After the 16week intervention, there was a significant decrease in visceral fat (VAT:total abdominal AT [as a %]; p = 0.002) and an increase in the Matsuda index (i.e. improved insulin sensitivity; p = 0.04) in the pioglitazone group relative to the placebo group. A significant increase in the formation of new adipocytes was observed in the scFEM (Δ = 3.3 ± 1.6%; p = 0.04) but not the scABD depot (Δ = 2.0 ± 2.1%; p = 0.32) in the pioglitazone group relative to the placebo group. No serious adverse events were reported. Pioglitazone may elicit distinct differences in in vivo adipogenesis in subcutaneous adipose depots in women with obesity, with increased rates in the protective scFEM. Trial registration ClinicalTrials.gov NCT01748994 Funding This study was funded by R01DK090607, P30DK072476, and R03DK112006 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health. The Robert C. and Veronica Atkins Foundation. Graphical abstract.

Ginsenoside Rg2 Ameliorates High-Fat Diet-Induced Metabolic Disease through SIRT1.

Ginsenoside Rg2 has been previously reported to reduce glucose production and adipogenesis in adipose tissue. However, the effects of ginsenosides Rg2 on hepatic lipid metabolism remain vacant. In this study, we found that ginsenoside Rg2 treatment significantly attenuated oleic acid and palmitic acid (OA&PA)-induced intracellular lipid deposition and oxidative stress in mouse primary hepatocytes. C57BL/6J mice that are fed with a high-fat diet (HFD) and treated with ginsenosides Rg2 displayed decreased body weight, reversed hepatic steatosis, and improved glucose tolerance and insulin sensitivity. Ginsenoside Rg2 administration significantly ameliorated HFD-induced hepatic oxidative stress and apoptosis. Moreover, Ginsenoside Rg2 had a good affinity with Sirtuin1 (SIRT1) and regulated its expression in vivo and in vitro. Deficiency of SIRT1 eliminated the therapeutic effect of ginsenoside Rg2 on lipid accumulation and overproduction of reactive oxygen species (ROS) in OA&PA-induced mice primary hepatocytes. Ginsenoside Rg2 treatment failed to alter the lipid and glucose disorder in hepatic SIRT1 deficient mice feeding on HFD. SIRT1 deficiency dissolves the therapeutic effect of ginsenoside Rg2 on oxidative stress and hepatocyte apoptosis induced by HFD. In summary, ginsenoside Rg2 plays a therapeutic role in HFD-induced hepatosteatosis of mice by decreasing the lipogenesis process and improving antioxidant capacity in an SIRT1-dependent manner.

Heme Oxygenase-1 Upregulation: A Novel Approach in the Treatment of Cardiovascular Disease

Significance: Heme oxygenase (HO) plays a pivotal role in both vascular and metabolic functions and is involved in many physiological and pathophysiological processes in vascular endothelial cells (ECs) and adipocytes. Recent Advances: From the regulation of adipogenesis in adipose tissue to the adaptive response of vascular tissue in the ECs, HO plays a critical role in the capability of the vascular system to respond and adjust to insults in homeostasis. Recent studies show that HO-1 through regulation of adipocyte and adipose tissue functions ultimately aid not only in local but also in systemic maintenance of homeostasis. Critical Issues: Recent advances have revealed the existence of a cross talk between vascular ECs and adipocytes in adipose tissue. In the pathological state of obesity, this cross talk contributes to the condition's adverse chronic effects, and we propose that specific targeting of the HO-1 gene can restore signaling pathways and improve both vascular and adipose functions. Future Directions: A complete understanding of the role of HO-1 in regulation of cardiovascular homeostasis is important to comprehend the homeostatic regulation as well as in cardiovascular disease. Efforts are required to highlight the effects and the ability to target the HO-1 gene in models of obesity with an emphasis on the role of pericardial fat on cardiovascular health.

The association between maternal nicotine exposure and adipose angiogenesis in female rat offspring: A mechanism of adipose tissue function changes

Maternal smoking during pregnancy and lactation is associated with increased fat mass in the offspring, but the mechanism by which this occurs is not fully understood. Our study focused on the relationships among maternal nicotine exposure, adipose angiogenesis and adipose tissue function in female offspring. Pregnant rats were randomly assigned to nicotine or control groups. Microvascular density, lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested in 4-, 12- and 26-week female offspring. In vitro, nicotine concentration- and time-response experiments were conducted in 3T3-L1. Lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested. The conditioned media of differentiated 3T3-L1 treated with nicotine were used to observe tube formation in human umbilical vein endothelial cells (HUVECs). Nicotine-exposed females presented higher adipose microvascular density. The gene expression of α7nAChR, Egr1 and FGF2 was significantly increased in gonadal white adipose tissue (gWAT) and inguinal subcutaneous WAT (igSWAT) of nicotine-exposed females at 4 weeks of age. The protein expression of α7nAChR, Egr1 and FGF2 was increased in gWAT and igSWAT of nicotine-exposed females at 4 weeks of age, and increased in gWAT at 26 weeks. In vitro, nicotine increased the expression of lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins in a concentration- and time-dependent manner. In the tube formation experiment, adipocytes affected by nicotine promoted HUVEC angiogenesis. Therefore, maternal nicotine exposure promoted the early angiogenesis of adipose tissue via the α7nAChR-Egr1-FGF2 signaling pathway, and this angiogenesis mechanism was associated with increased adipogenesis in adipose tissue of female offspring.

Mangifera indica leaves extract and mangiferin modulate CB1 and PPARγ receptors and others markers associated with obesity

Abstract This study aimed phytochemical characterization (UPLC-DAD-MS/MS) of ethanolic extract of the leaves from Mangifera indica (EMI) and Mangiferin (MAN), analysis of the cytotoxic (MTT) and anti-inflammatory potential (expression of TNF-α) of EMI and MAN in vitro. In addition, was evaluate the effect on the mRNA expression of genes (CB1, PPARγ, adiponectin, resistin and leptin) associated with adipogenesis in adipose tissue of rats fed a cafeteria diet. Thus, wistar rats were treated by gavage with EMI and MAN for several days (according to the post and co-treatments). The adipose tissue was weighed and checked the expression of different markers by RT-PCR. The presence of MAN as major compound in EMI was verified. Both EMI and MAN were not cytotoxic, with lower EMI expression of TNF-α. Furthermore, EMI and MAN had proadipogenic action on post-treatment, while in the co-treatment, EMI attenuated the effect of adipogenesis and MAN increased the adipogenic process.

High fat diet aggravates cardiomyopathy in murine chronic Chagas disease

Infection with Trypanosoma cruzi, the etiologic agent in Chagas disease, may result in heart disease. Over the last decades, Chagas disease endemic areas in Latin America have seen a dietary transition from the traditional regional diet to a Western style, fat rich diet. Previously, we demonstrated that during acute infection high fat diet (HFD) protects mice from the consequences of infection-induced myocardial damage through effects on adipogenesis in adipose tissue and reduced cardiac lipidopathy. However, the effect of HFD on the subsequent stages of infection – the indeterminate and chronic stages – has not been investigated. To address this gap in knowledge, we studied the effect of HFD during indeterminate and chronic stages of Chagas disease in the mouse model. We report, for the first time, the effect of HFD on myocardial inflammation, vasculopathy, and other types of dysfunction observed during chronic T. cruzi infection. Our results show that HFD perturbs lipid metabolism and induces oxidative stress to exacerbate late chronic Chagas disease cardiac pathology.

Chick subcutaneous and abdominal adipose tissue depots respond differently in lipolytic and adipogenic activity to α-melanocyte stimulating hormone (α-MSH)

In birds, α-MSH is anorexigenic, but effects on adipose tissue are unknown. Four day-old chicks were intraperitoneally injected with 0 (vehicle), 5, 10, or 50μg of α-MSH and subcutaneous and abdominal adipose tissue collected at 60min for RNA isolation (n=10). Plasma was collected post-euthanasia at 60 and 180min for measuring non-esterified fatty acids (NEFA) and α-MSH (n=10). Relative to the vehicle, food intake was reduced in the 50μg-treated group. Plasma NEFAs were greater in 10μg than vehicle-treated chicks at 3h. Plasma α-MSH was 3.06±0.57ng/ml. In subcutaneous tissue, melanocortin receptor 5 (MC5R) mRNA was increased in 10μg, MC2R and CCAAT-enhancer-binding protein β (C/EBPβ) mRNAs increased in 50μg, peroxisome proliferator-activated receptor γ and C/EBPα decreased in 5, 10 and 50μg, and Ki67 mRNA decreased in 50μg α-MSH-injected chicks, compared to vehicle-injected chicks. In abdominal tissue, adipose triglyceride lipase mRNA was greater in 10μg α-MSH- than vehicle-treated chicks. Cells isolated from abdominal fat that were treated with 10 and 100nM α-MSH for 4h expressed more MC5R and perilipin-1 than control cells (n=6). Cells that received 100nM α-MSH expressed more fatty acid binding protein 4 and comparative gene identification-58 mRNA than control cells. Glycerol-3-phosphate dehydrogenase (G3PDH) activity was greater in cells at 9days post-differentiation that were treated with 1 and 100nM α-MSH for 4h than in control cells (n=3). Results suggest that α-MSH increases lipolysis and reduces adipogenesis in adipose tissue.

Dietary overload lithium decreases the adipogenesis in abdominal adipose tissue of broiler chickens.

To investigate the toxic effects of dietary overload lithium on the adipogenesis in adipose tissue of chicken and the role of hypothalamic neuropeptide Y (NPY) in this process, one-day-old male chicks were fed with the basal diet added with 0 (control) or 100mg lithium/kg diet from lithium chloride (overload lithium) for 35days. Abdominal adipose tissue and hypothalamus were collected at day 6, 14, and 35. As a percentage of body weight, abdominal fat decreased (p<0.001) at day 6, 14, and 35, and feed intake and body weight gain decreased during day 7-14, and day 15-35 in overload lithium treated broilers as compared to control. Adipocyte diameter and DNA content in abdominal adipose tissue were significantly lower in overload-lithium treatment than control at day 35, although no significant differences were observed at day 6 and 14. Dietary overload lithium decreased (p<0.01) transcriptional expression of preadipocyte proliferation makers ki-67 (KI67), microtubule-associated protein homolog (TPX2), and topoisomerase 2-alpha (TOP2A), and preadipocyte differentiation transcriptional factors peroxisome proliferator-activated receptor-γ (PPARγ), and CCAAT/enhancer binding protein (C/EBP) α mRNA abundance in abdominal adipose tissue. In hypothalamus, dietary overload lithium influenced (p<0.001) NPY, and NPY receptor (NPYR) 6 mRNA abundance at day 6 and 14, but not at day 35. In conclusion, dietary overload lithium decreased the adipogenesis in abdominal adipose tissue of chicken, which was accompanied by depressing transcriptional expression of adipogenesis-associated factors. Hypothalamic NPY had a potential role in the adipogenesis in abdominal adipose tissue of broilers with a short-term overload lithium treatment.

Fermented Platycodon grandiflorum Extract Inhibits Lipid Accumulation in 3T3-L1 Adipocytes and High-Fat Diet-Induced Obese Mice.

The aim of this study was to investigate whether fermented Platycodon grandiflorum (FPG) inhibits lipid accumulation in 3T3-L1 adipocytes and mice with high-fat diet (HFD)-induced obesity. We evaluated the effect of FPG on antiadipogenic activity via regulation of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), as well as protein expression of their target genes, fatty acid binding protein 4 (FABP4). We further examined the antiobesity effects of FPG on HFD-induced obesity in mice. The FPG was orally administered to mice with a HFD at 50, 100, or 200 mg/kg/day for 8 weeks. Our results show that FPG significantly inhibited fat accumulation during 3T3-L1 adipogenesis through downregulating adipogenic transcript factors. Moreover, FPG markedly reduced the final body weight with a decrease in epididymal adipose tissue mass and adipocyte size compared with the untreated HFD-induced group. The effects of FPG on HFD-induced obesity were primarily responsible for inhibiting adipogenesis in adipose tissue and regulating lipid metabolism, such as through lipogenesis and fatty acid oxidation. Additionally, FPG ameliorated serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. Hence, FPG may be an alternative treatment for controlling obesity through downregulating lipid accumulation.

Impaired adipogenesis in adipose tissue associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet.

Chronic inflammation might be associated with hepatic lipid deposition independent of overnutrition. However, the mechanism is not fully understood. In this study, we investigate if impaired adipogenesis in adipose tissue is associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet. Casein injection in C57BL/6J mice was given every other day to induce chronic inflammation. All mice were sacrificed after 18weeks of injections. The serum, liver and adipose tissue were collected for analysis. Real-time polymerase chain reaction and western blotting were used to examine the gene and protein expressions of molecules involved in hepatic lipid metabolism and adipose adipogenesis. Casein injection elevated serum levels of insulin, free fatty acid (FFA) and proinflammatory factors. The gene expression of proinflammatory factors of adipose tissue and the liver also increased in the casein group as compared with the control group. Chronic inflammation up-regulated the hepatic expression of fatty acid translocase (CD36) and down-regulated microsomal triacylglycerol transfer protein (MTP), carnitine palmitoyltransferase 1a (CPT1a) and acyl-coenzyme a oxidase 1 (ACOX1). Meanwhile, chronic inflammation not only diminished the size of adipocytes, but also down-regulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding proteinα (C/EBPα), both indicating an impaired adipogenesis. Besides disturbed lipid metabolism in the liver per se, impaired adipogenesis in the adipose tissue might also be associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet.

Effect of high hydrostatic pressure extract of Korean ginseng on adipogenesis in 3T3‐L1 adipocytes (1045.4)

Ginseng, especially steam‐and‐dry processed red ginseng, has been shown to decrease adipogenesis in adipose tissue. In the food processing industry, high hydrostatic pressure extraction technique has become an alternative to heat processing. The aim of this study was to comparatively investigate the anti‐adipogenic effects of water extract of red ginseng (WRG) and high hydrostatic pressure extract of fresh ginseng (HPG) in 3T3‐L1 adipocytes. Intracellular lipid and triglyceride were decreased in both WRG and HPG treated cells, while the cell viability remained unaffected. This observed decrease was consistent with the reduction of GPDH activity, a key enzyme in triglyceride biosynthesis. The mRNA expressions of adipogenic genes, including peroxisome proliferator‐activated receptor‐gamma, CCAAT/enhancer‐binding protein‐α, sterol regulatory element‐binding protein‐1c, and adipocyte fatty acid binding protein, were significantly decreased in both WEG and HPG treated cells. The activity of AMPK, a key regulator of energy metabolism, was significantly increased in the HPG treated cells compared to the WRG. From these results, it is assumed that anti‐adipogenic mechanisms of the WRG and HPG in adipocytes might be associated with inhibition of GPDH activity and adipogenic gene expression as well as AMPK activation. Moreover, efficiency of the HPG might be comparable to that of the WRG.Grant Funding Source: This work was supported by the Brain Korea 21 plus project funding (No. 22A20130012143)

Prostaglandin J2 series induces the gene expression of monocyte chemoattractant protein-1 during the maturation phase of cultured adipocytes

Prostaglandin (PG) J2 series including Δ12-PGJ2 and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is the dehydration products of PGD2 that are biosynthesized through the cyclooxygenase (COX) pathway. These prostanoids are active ligands for peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis in adipocytes. Here we investigated whether PGJ2 derivatives can modulate the gene expression of monocyte chemoattractant protein-1 (MCP-1), a pro-inflammatory chemokine, during the maturation phase of adipocytes. Each of selective or nonselective inhibitors for COX isoforms suppressed significantly the accumulation of fats by interfering the induced expression of the PPARγ gene. Immunological assays of PGJ2 series revealed higher production of Δ12-PGJ2 than 15d-PGJ2 by cultured adipocytes, implicating the contribution of endogenous PGJ2 series to the stimulated adipogenesis. In addition, the increased transcription of MCP-1 was detectable at later maturation phase of adipogenesis, which was prevented by co-incubation with aspirin. Although 15d-PGJ2 was more potent than Δ12-PGJ2, both PGJ2 derivatives series had similar effects to rescue dose-dependently the expression of the MCP-1 gene attenuated by aspirin. These findings suggest that the expression of MCP-1 involved in adipocyte inflammation could be positively regulated by the PGJ2 series during adipogenesis in adipose tissue.

β-Arrestin-1 Protein Represses Diet-induced Obesity

Diet-related obesity is a major metabolic disorder. Excessive fat mass is associated with type 2 diabetes, hepatic steatosis, and arteriosclerosis. Dysregulation of lipid metabolism and adipose tissue function contributes to diet-induced obesity. Here, we report that β-arrestin-1 knock-out mice are susceptible to diet-induced obesity. Knock-out of the gene encoding β-arrestin-1 caused increased fat mass accumulation and decreased whole-body insulin sensitivity in mice fed a high-fat diet. In β-arrestin-1 knock-out mice, we observed disrupted food intake and energy expenditure and increased macrophage infiltration in white adipose tissue. At the molecular level, β-arrestin-1 deficiency affected the expression of many lipid metabolic genes and inflammatory genes in adipose tissue. Consistently, transgenic overexpression of β-arrestin-1 repressed diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Thus, our findings reveal that β-arrestin-1 plays a role in metabolism regulation.

Rubus suavissimus S. Lee extract increases early adipogenesis in 3T3-L1 preadipocytes

Leaves of Rubus suavissimus S. Lee (Rosaceae) are used to prepare tiencha or sweet tea, which is helpful for body weight control by restricting calorie intake in obese patients. Obesity is a risk factor for metabolic syndrome, and a possible approach to treatment is to promote early adipogenesis in adipose tissue, thereby leading to replacement of enlarged adipocytes that secrete inflammatory factors with small adipocytes.We therefore investigated the effect of extract of tiencha leaves on early adipogenesis by using 3T3-L1 preadipocytes as a model. Tiencha extract significantly and concentration-dependently increased adipogenesis measured in terms of lipid accumulation by means of Oil Red O assay and increased the expression of adiponectin and leptin. In the early phase of adipogenesis, tiencha extract increased the mRNA expression of adipogenic transcription factors CCAAT/enhancer binding protein α (C/EBPα) and proliferator-activated receptor γ (PPARγ). In contrast, mRNA expression of other adipogenic transcription factors, C/EBPδ and C/EBPβ, was unaffected. The mRNA expression levels of adipocyte-specific genes encoding adipocyte protein 2 (aP2), lipoprotein lipase (LPL), and glucose transporter 4 (Glut4), which are regulated by C/EBPα and PPARγ, were also increased. A PPARγ inhibitor, GW9662, partially inhibited the enhancing effect of tiencha extract on lipogenesis. These results suggest that tiencha extract enhances early adipogenesis by increasing the expression of adipogenic transcription factors C/EBPα and PPARγ.