Regulation of Adipocyte Formation by GLP-1/GLP-1R Signaling

Challa, Tenagne D.; Beaton, Nigel; Arnold, Myrtha; Rudofsky, Gottfried; Langhans, Wolfgang; Wolfrum, Christian

doi:10.1074/jbc.m111.310342

Cited by 113 publications

(98 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, a recent study suggests that GLP-1 promotes the proliferation and differentiation of preadipocytes by GLP-1R (28). The results of the present study support the latter view.…”

Section: Discussionsupporting

confidence: 82%

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

Yang

Ren

Song

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

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...

show abstract

“…However, a recent study suggests that GLP-1 promotes the proliferation and differentiation of preadipocytes by GLP-1R (28). The results of the present study support the latter view.…”

Section: Discussionsupporting

confidence: 82%

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

Yang

Ren

Song

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

show abstract

“…Subcutaneous, visceral, and 3T3-L1 preadipocytes were grown and induced to differentiate with induction medium containing 10 mg/mL insulin, 10 mmol/L dexamethasone, 11.5 mg/mL isobutylmethylxanthine, and 10% FBS as described previously (16,17,20,21) for a total of 10 days. For validation of the preadipocyte differentiation method, confluent cells were treated with or without rosiglitazone during induction of differentiation and adipocyte formation was quantified using automated image-based analysis (16,17,20,21).…”

Section: Differentiation Of Preadipocytesmentioning

confidence: 99%

“…Preadipocytes were cultured for 24 h with siRNA; afterward, the medium was changed to regular medium. After the differentiation procedure, automated differentiation quantification was performed (16,17,20,21). Custom library siRNA was purchased from Dharmacon (Wohlen, Switzerland) and Microsynth (Balgach, Switzerland) (sequences available upon request).…”

Section: Reverse Transfection Of Preadipocytesmentioning

confidence: 99%

“…1B). 3T3-L1 cells and primary subcutaneous and visceral preadipocytes were cultured on the bottom chambers of sixwell plates at the density of 4.66 3 10 5 , 8.7 3 10 6 , and 8.7 3 10 6 cells/well as described previously (16,17). SA, SE, VA, or VE were cultured separately on the insert for 48 h. Preadipocytes were cultured for 3 days and then SA, SE, VA, or VE were transferred to the culture plates and cocultured together ( Supplementary Fig.…”

Section: Coculture Experimentsmentioning

confidence: 99%

“…For validation of the preadipocyte differentiation method, confluent cells were treated with or without rosiglitazone during induction of differentiation and adipocyte formation was quantified using automated image-based analysis (16,17,20,21).…”

Section: Differentiation Of Preadipocytesmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of De Novo Adipocyte Differentiation Through Cross Talk Between Adipocytes and Preadipocytes

et al. 2015

Self Cite

View full text Add to dashboard Cite

There are many known adipokines differentially secreted from the different adipose depots; however, their paracrine and autocrine effects on de novo adipocyte formation are not fully understood. By developing a coculture method of preadipocytes with primary subcutaneous and visceral adipocytes or tissue explants, we could show that the total secretome inhibited preadipocyte differentiation. Using a proteomics approach with fractionated secretome samples, we were able to identify a spectrum of factors that either positively or negatively affected adipocyte formation. Among the secreted factors, Slc27a1, Vim, Cp, and Ecm1 promoted adipocyte differentiation, whereas Got2, Cpq, interleukin-1 receptor-like 1/ST2-IL-33, Sparc, and Lgals3bp decreased adipocyte differentiation. In human subcutaneous adipocytes of lean subjects, obese subjects, and obese subjects with type 2 diabetes, Vim and Slc27a1 expression was negatively correlated with adipocyte size and BMI and positively correlated with insulin sensitivity, while Sparc and Got2 showed the opposite trend. Furthermore, we demonstrate that Slc27a1 was increased upon weight loss in morbidly obese patients, while Sparc expression was reduced. Taken together, our findings identify adipokines that regulate adipocyte differentiation through positive or negative paracrine and autocrine feedback loop mechanisms, which could potentially affect whole-body energy metabolism.

show abstract

Semaglutide (GLP‐1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice

Martins

Marinho

Cardoso

et al. 2022

Cell Biochemistry & Function

View full text Add to dashboard Cite

Semaglutide (GLP-1 agonist) was approved for treating obesity. Although the effects on weight loss and metabolism are known, the responses of adipocytes to semaglutide are yet limited. C57BL/6 male mice (n = 20/group) were fed a control diet (C) or a high-fat (HF) diet for 16 weeks and then separated into four groups (n = 10/group) for an additional four weeks: C, C diet and semaglutide, HF, and HF diet and semaglutide. Epididymal white adipose tissue (eWAT) and subcutaneous white adipose tissue (sWAT) fat pads were studied with biochemistry, immunohistochemistry/fluorescence, stereology, and reverse transcription-quantitative polymerase chain reaction. In obese mice, semaglutide reduced the fat pad masses (eWAT, −55%; sWAT, −40%), plasmatic cytokines, and proinflammatory gene expressions: tumor necrosis factor-alpha (−60%); interleukin (IL)-6 (−55%); IL-1 beta (−40%); monocyte chemoattractant protein-1 (−90%); and leptin (−80%). Semaglutide also lessened endoplasmic reticulum (ER) stress genes of activating transcription factor-4 (−85%), CCAAT enhancer-binding protein homologous protein (−55%), and growth arrest and DNA damage-inducible gene 45 (−45%). The obese mice's adipocyte hypertrophy and macrophage infiltration were equally reduced by semaglutide. Semaglutide enhanced multiloculation and uncoupled protein 1 (UCP1) labeling in obese mice: peroxisome proliferator-activated receptor-alpha (+560%) and gamma (+150%), fibronectin type III domain-containing protein 5 (+215%), peroxisome proliferator-activated receptor-alpha coactivator (+110%), nuclear respiratory factor 1 (+260%), and mitochondrial transcription factor A (+120%). Semaglutide also increased thermogenetic gene expressions for the browning phenotype maintenance: beta-3 adrenergic receptor (+520%), PR domain containing 16 (+90%), and Ucp1 (+110%). In conclusion, semaglutide showed significant beneficial effects beyond weight loss, directly on fat pads and adipocytes

show abstract

Regulation of Adipocyte Formation by GLP-1/GLP-1R Signaling

Cited by 113 publications

References 51 publications

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

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

Regulation of De Novo Adipocyte Differentiation Through Cross Talk Between Adipocytes and Preadipocytes

Semaglutide (GLP‐1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice

Contact Info

Product

Resources

About