Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Abstract

Abstract. Glucagon-like peptide 1 (GLP-1), a gut-derived peptide, has been reported to have profound effects on metabolism and to reduce insulin resistance. Adipocyte hyperplasia stimulated by preadipocyte differentiation has a positive effect on adipose tissue insulin sensitivity. However, it remains less clear whether GLP-1 plays a role in adipogenesis. In this study, we examined the effect of GLP-1 on preadipocyte differentiation and investigated the mechanisms that may be involved in this effect. In our 3T3-L1 cell study, we tested the levels of adipocyte-specific markers and signaling pathways during preadipocyte differentiation. In addition, Oil Red O staining was used to examine lipid accumulation. Image Pro Plus 5.02 was used to analyze the size and number of lipid droplets. We found that GLP-1 elevated the protein expression levels of free fatty acid-binding protein 4 (aP2) and the transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ) in a dose-dependent manner during 3T3-L1 preadipocyte differentiation. Furthermore, RT-PCR results showed that GLP-1 promoted CCAAT/enhancer-binding protein α (C/EBPα) and lipoprotein lipase (LPL) expression at the transcriptional level. These data suggest that GLP-1 promotes preadipocyte differentiation. Our study also found that treatment of the cells with 100 nM GLP-1 enhanced the phosphorylation of Akt signaling during the first 24 h of differentiation. Although Oil Red O staining showed that GLP-1 had no significant effect on lipid accumulation, there were increased numbers of small adipocytes in the cells treated with 100 nM GLP-1. Taken together, these results indicate that GLP-1 regulates 3T3-L1 adipogenesis and the Akt signaling pathway may be involved in this process. The differentiated small adipocytes may have a positive effect against insulin resistance and obesity. IntroductionThe growing prevalence of obesity constitutes a major health problem worldwide (1). Obesity, particularly abdominal obesity, has a strong relationship with insulin resistance and is a major risk factor for type 2 diabetes and cardiovascular disease (2,3). The imbalance between energy intake and expenditure contributes to the development of obesity (1,4); the cellular mechanisms for which include the expansion of white adipose tissue via the hypertrophy of preexisting adipocytes and hyperplasia resulting from the adipogenesis of preadipocytes (4,5). When animals are maintained on a highfat diet, adipo cyte cell size initially increases, followed by an increase in fat cell number upon prolonged over-nutrition (6). In adults, ~10% of fat cells are renewed from preadipocytes annually (7). One study in adults demonstrated that short-term overfeeding increases the adipocyte cell numbers (8). Thus, adipogenesis probably has a role in the pathology of obesity in human adults. However, there are significant differences in lipid and glucose metabolism between adipocyte hypertrophy and hyperplasia (9-11). Recent studies have shown that adipocyte hypertrophy is negatively corre...

GLP-1/GLP-1R Signaling in Regulation of Adipocyte Differentiation and Lipogenesis

“…To explore the possible roles of GLP-1/ GLP-1R in adipogenesis and lipid metabolism, we first examined the expression profile of GLP-1R in 3T3-L1 adipocytes. Consistent with previous observations [43,44], we confirmed the presence of GLP-1R in both preadipocytes and differentiated adipocytes. Interestingly, we found that GLP-1R expression in both mRNA and protein levels decrease along with the differentiation, which may imply that GLP-1/GLP-1R signaling could play more important roles in undifferentiated adipocytes.…”

Effects of glucagon‐like peptide‐1 on the differentiation and metabolism of human adipocytes

“…Finally, we also investigated the effect of GLP‐1 on Akt and ERK, intracellular signalling pathways that have been reported to be activated by GLP‐1 in adipocytes and other cell types (Challa et al ., ; Yang et al ., ). Neither Akt nor ERK1/2 phosphorylation rates were modified after 5 or 30 min of exposure of differentiated 3T3‐L1 cells to GLP‐1 (Figure S1B).…”

Anti‐obesogenic effects of calcium prevent changes in the GLP‐1 profile in adult rats primed by early weaning

“…Some studies have associated ghrelin and GLP‐1 with adipogenesis. Both GI hormones stimulate adipogenesis; ghrelin acts mainly on insulin sensitivity and GLP‐1 induces adipogenesis by stimulating differentiation of and inhibiting apoptosis of preadipocytes . These data suggest that these hormones may have a cross‐talk effect on adipogenesis.…”