Enhancement Of Adipogenesis Research Articles

Gallic acid regulates adipocyte hypertrophy and suppresses inflammatory gene expression induced by the paracrine interaction between adipocytes and macrophages in vitro and in vivo

Obesity-induced chronic inflammation in adipose tissue plays a critical role in the development of insulin resistance and various lifestyle-related diseases. Although gallic acid (GA) is known to exert protective effects on obesity-related complications, its function in adipose tissue inflammation has not been elucidated. Recently, we reported that GA exerts protective effects against inflammation. To test our hypothesis that the anti-inflammatory effect of GA partially contributes to the improvement of metabolic diseases, we examined the effect of GA on inflammation caused by adipocyte-macrophage crosstalk in obesity. We showed that GA enhanced adipocyte differentiation in 3 T3-L1 adipocytes. Consistent with the enhancement of adipogenesis, GA decreased the gene expression of monocyte chemoattractant protein-1 and increased that of adiponectin and the upstream mediator peroxisome proliferator-activated receptor gamma. GA also reduced inflammatory mediator expression induced by the co-culture of 3 T3-L1 adipocytes with RAW 264 macrophages. Diet-induced obese mice treated with GA showed decreased serum cholesterol levels and adipocyte size, and improved insulin sensitivity without changes in body weight. Moreover, GA-treated mice had decreased expression of interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, F4/80, and sterol regulatory element binding transcription factor-1 in their adipose tissue. These results indicate that GA suppresses adipocyte hypertrophy and inflammation caused by the interaction between adipocytes and macrophages, thereby improving metabolic disorders such as insulin resistance and dyslipidemia.

Regulation of PKCβ levels and autophagy by PML is essential for high-glucose-dependent mesenchymal stem cell adipogenesis

Obesity is a complex disease characterized by the accumulation of excess body fat, which is caused by an increase in adipose cell size and number. The major source of adipocytes comes from mesenchymal stem cells (MSCs), although their roles in obesity remain unclear. An understanding of the mechanisms, regulation, and outcomes of adipogenesis is crucial for the development of new treatments for obesity-related diseases. Recently an unexpected role for the tumor suppressor promyelocytic leukemia protein (PML) in hematopoietic stem cell biology and metabolism regulation has come to light, but its role in MSC biology remains unknown. Here, we investigated the molecular pathway underlying the role of PML in the control of adipogenic MSC differentiation. Muscle-derived stem cells (MDSCs) and adipose-derived stem cells (ADSCs) obtained from mice and voluntary patients (as a source of MSCs) were cultured in the presence of high glucose (HG) concentration, a nutrient stress condition known to promote MSCs differentiation into mature adipocytes and the adipogenic potential of PML was assessed. PML is essential for a correct HG-dependent adipogenic differentiation, and the enhancement of PML levels is fundamental during adipogenesis. Increased PML expression enables the upregulation of protein kinase Cβ (PKCβ), which, in turn, by controlling autophagy levels permits an increase in peroxisome proliferator-activated receptor γ (PPARγ) that leads the adipogenic differentiation. Therefore, genetic and pharmacological depletion of PML prevents PKCβ expression, and by increasing autophagy levels, impairs the MSCs adipogenic differentiation. Human ADSCs isolated from overweight patients displayed increased PML and PKCβ levels compared to those found in normal weight individuals, indicating that the PML-PKCβ pathway is directly involved in the enhancement of adipogenesis and human metabolism. The new link found among PML, PKCβ, and autophagy opens new therapeutic avenues for diseases characterized by an imbalance in the MSCs differentiation process, such as metabolic syndromes and cancer.

AIDA Selectively Mediates Downregulation of Fat Synthesis Enzymes by ERAD to Retard Intestinal Fat Absorption and Prevent Obesity

The efficiency of intestinal absorption of dietary fat constitutes a primary determinant accounting for individual vulnerability to obesity. However, how fatabsorption is controlled and contributes to obesity remains unclear. Here, we show that inhibition of endoplasmic-reticulum-associated degradation (ERAD) increases the abundance of triacylglycerol synthesis enzymes and fat absorption in smallintestine. The C2-domain protein AIDA acts as an essential factor for the E3-ligase HRD1 of ERAD to downregulate rate-limiting acyltransferases GPAT3, MOGAT2, and DGAT2. Aida-/- mice, whengrown in a thermal-neutral condition or fed high-fat diet, display increased intestinal fatty acid re-esterification,circulating and tissue triacylglycerol, accompanied with severely increased adiposity without enhancement of adipogenesis. Intestine-specific knockout of Aida largely phenocopies its whole-body knockout, strongly indicating that increased intestinal TAG synthesis is a primary impetus to obesity. The AIDA-mediated ERAD system may thus represent an anti-thrifty mechanism impinging on the enzymes for intestinal fat absorption and systemic fat storage.

Impairment of primary cilia contributes to visceral adiposity of high fat diet-fed mice.

Deficiency of primary cilia formation by knockout kinesin family member 3A (Kif3a) in mature osteoblasts led to osteopenia and enhanced adipogenesis. Adipogenesis plays an important role in adipose tissue expansion by High-fat-diet (HFD) induced obesity. Whether primary cilia participate in high-fat-diet induced adiposity remains unclear. In this study, we found that the number and length of primary cilia and expression levels of KIF3A and intraflagellar transport 88 homolog (IFT88) mRNA and proteins reached peak on the day 3 of adipogenesis, followed by a decrease to reach low basal expression levels at day 9 when differentiated to lipid accumulating adipocytes in VAT-SVFs derived from lean mice. The number of primary cilia was reduced by shRNA and chemical methods, leading to elevated transcripts of Pparγ, Cebp-α, Srebp-1, and Fasn and protein levels of PPARγ and FASN. Similar to the proadipogenic effect by the inhibition of primary cilia formation in control VAT-SVFs, HFD caused severe reduction of primary cilia formation and enhancement of adipogenesis in VAT-SVFs cultures. Flow cytometry analysis revealed percentage of G2/M phase cells and the protein expression of Cyclin A2 and CDK2 increased in control VAT-SVFs by knockdown of primary cilia with shRNA or chemical methods and HFD induced obese VAT-SVFs. In conclusion, the expression of primary cilia was in reverse correlation with adipogenic differentiation. HFD caused severe defects of primary cilia in VAT-SVFs, leading to adipose tissue expansion by enhancement of adipogenesis through promoting cell cycle re-entry at the early stage of adipogenesis.

The potential contribution of adenovirus 36 to the development of obesity

The evidence of the last 20 years shows a link between viral infections and obesity in animals and humans. There are five adenovirus which have been associated with development of obesity in animals. SMAM-1 virus was the first studied in humans associated with obesity. There is compelling evidence that Ad-36 virus could contribute to the development of obesity in humans and it is related with body mass index (BMI). This manuscript reviews the association between Ad-36 and the other four virus infections with obesity. An electronic search of articles in the databases PubMed and Scielo, with use of key words: obesity, infection, adipose tissue, Ad-36, 3T3-L1 was performed. The search was restricted "human" and "animals". The importance of the relationship between virus infections and obesity has increased over the past two decades. Ad-36 shows more compelling evidence in humans. There are reports involving this virus in the enhancement of adipogenesis, adipocyte differentiation, a lower secretion of leptin and an increased insulin sensitivity. Future work should focus in larger cohort studies to confirm this association, which explains the global obesity epidemic from a new perspective.

Epigenetic landscape in PPARγ2 in the enhancement of adipogenesis of mouse osteoporotic bone marrow stromal cell

Epigenetic landscape in PPARγ2 in the enhancement of adipogenesis of mouse osteoporotic bone marrow stromal cell

Enhancement of adipogenesis and fibrogenesis in skeletal muscle of Wagyu compared with Angus cattle

Intramuscular fat and collagen content are major factors affecting beef quality, but mechanisms regulating intramuscular adipose and connective tissue deposition are far from clear. Japanese Wagyu cattle are well known for their extremely high marbling. The objective of this study was to evaluate intramuscular fat (IMF) and collagen deposition in the muscle of Wagyu compared with Angus cattle. Animals were managed under the same condition and slaughtered at an averaging 585 ± 12.1 kg of BW. Samples of sternomandibularis muscle were collected from Wagyu (n = 3) and Angus (n = 3) for molecular and histological investigations of adipogenesis and fibrogenesis. With exception of C/EBPβ (P = 0.2864), the expression of the adipogenic markers C/EBPα (P = 0.008), PPARγ (P = 0.028), and zip finger protein 423 (Zfp423; P = 0.047) in Wagyu were greater than in Angus muscle, which was consistent with greater IMF deposition in Wagyu (P < 0.05). In addition, more adipocytes and preadipocytes were detected intramuscularly in Wagyu cattle. Similarly, fibrogenesis was also enhanced in Wagyu, with a greater expression of fibroblast growth factor (FGF)-2 (P = 0.028), FGF receptor 1 (P = 0.030), transforming growth factor (TGF)-β (P = 0.028), collagen I (P = 0.012), and collagen III (P = 0.025). Similarly, Wagyu muscle had greater collagen content (P = 0.002) and decreased collagen solubility (P = 0.005). In addition, muscle fiber diameter was larger (P < 0.0001) in Wagyu than in Angus cattle. These results clearly show that both IMF and collagen contents are enhanced in Wagyu cattle and more adipogenic cells are detected in Wagyu muscle, indicating intramuscular adipogenesis is enhanced in Wagyu compared with Angus muscle.

Spinal cord injury causes bone loss through peroxisome proliferator‐activated receptor‐γ and Wnt signalling

It has long been recognized that spinal cord injury (SCI) leads to a loss of bone mineral. However, the mechanisms of bone loss after SCI remain poorly understood. The aim of this study was to investigate whether SCI causes a shift in skeletal balance between osteoblastogenesis and adipogenesis. Eighty male Sprague-Dawley rats at 6 weeks of age were randomly divided into two groups: sham-operated (SHAM) group and SCI group. The rats were killed after 3 weeks, 3 months and 6 months, and their femora, tibiae and humeri were collected for mesenchymal stem cells (MSCs) culture, bone mineral density (BMD) measurement, RNA analysis and Western Blot analysis. Osteogenic and adipogenic differentiation potential of MSCs from SCI rats and SHAM rats was evaluated. We found increased marrow adiposity in sublesional tibiae of SCI rats. SCI caused increased peroxisome proliferator-activated receptor-γ (PPARγ) expression and diminished Wnt signalling in sublesional tibiae. Interestingly, in MSCs from SCI rats treated with the PPARγ inhibitor GW9662, the ratios of RANKL to OPG expression were significantly decreased. On the contrary, in MSCs from SCI rats treated with the PPARγ ligand troglitazone, the ratios of RANKL to OPG expression in SCI rats were significantly increased. High expression of PPARγ may lead to increased bone resorption through the RANKL/OPG axis after SCI. In addition, high expression also results in the suppression of osteogenesis and enhancement of adipogenesis in SCI rats. SCI causes a shift in skeletal balance between osteoblastogenesis and adipogenesis, thus leading to bone loss after SCI.

Transcriptional Repression of pref-1by Glucocorticoids Promotes 3T3-L1 Adipocyte Differentiation

Pref-1 is an epidermal growth factor-like domain-containing transmembrane protein that is cleaved to generate a soluble factor. It is abundant in 3T3-L1 preadipocytes but absent in mature adipocytes. Constitutive expression of pref-1 or the addition of its ectodomain inhibits adipogenesis. We find that the pref-1 gene is an early target of dexamethasone, a component of the dexamethasone/methylisobutylxanthine differentiation mixture used routinely for adipoconversion. The time course of the decrease in pref-1 mRNA by dexamethasone reflected the pref-1 mRNA half-life determined by actinomycin D treatment. Nuclear run-on assays showed that dexamethasone attenuates pref-1 transcription. We demonstrate a correlation between pref-1 down-regulation and adipoconversion by varying the time period and concentration of dexamethasone. Increasing the dexamethasone treatment from 2 to 4 days resulted in a time-dependent pref-1 down-regulation and increased differentiation as measured by adipocyte marker mRNAs. The dexamethasone concentration between 1 and 10 nM showed a dose-dependent decrease in pref-1 mRNA and an enhancement of adipogenesis. To test the hypothesis that dexamethasone initiation of adipoconversion may be via down-regulation of pref-1, we lowered endogenous pref-1 mRNA levels by stably transfecting 3T3-L1 preadipocytes with antisense pref-1. At 1 microM, antisense cells had enhanced adipose conversion; a similar degree of differentiation occurred with 2 nM dexamethasone, a concentration that does not support differentiation of control 3T3-L1 cells. We conclude that dexamethasone-mediated repression of pref-1 contributes to the mechanisms whereby glucocorticoids promote adipogenesis.