Insulin-like growth factor 2 promotes adipocyte proliferation, differentiation and lipid deposition in obese type 2 diabetes

Luo, Xin; Ma, Jun; Yu, Miao; Yang, Zhenxing; Huang, Yongmin; Guo, Caiyun; Yang, Ling; Lü, Yan; Shi, Songqing

doi:10.15761/jts.1000362

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…Insulin exposure increases the steady-state number of IGF2R, in addition to increasing the ligation, internalization, and degradation of IGF2 [ 64 , 65 ]. These findings are curious due to the high levels of IGF2 expression in obese individuals with type 2 diabetes mellitus and because high doses of IGF2 increase in vitro differentiation and lipid accumulation [ 66 , 67 ]. Furthermore, Igf2r-KO directly reduced brown adipogenesis and brown adipocyte survival [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Proteogenomic Analysis Reveals Proteins Involved in the First Step of Adipogenesis in Human Adipose-Derived Stem Cells

Bonilauri

Camillo-Andrade

Santos

et al. 2021

Stem Cells International

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Background. Obesity is characterized as a disease that directly affects the whole-body metabolism and is associated with excess fat mass and several related comorbidities. Dynamics of adipocyte hypertrophy and hyperplasia play an important role in health and disease, especially in obesity. Human adipose-derived stem cells (hASC) represent an important source for understanding the entire adipogenic differentiation process. However, little is known about the triggering step of adipogenesis in hASC. Here, we performed a proteogenomic approach for understanding the protein abundance alterations during the initiation of the adipogenic differentiation process. Methods. hASC were isolated from adipose tissue of three donors and were then characterized and expanded. Cells were cultured for 24 hours in adipogenic differentiation medium followed by protein extraction. We used shotgun proteomics to compare the proteomic profile of 24 h-adipogenic, differentiated, and undifferentiated hASC. We also used our previous next-generation sequencing data (RNA-seq) of the total and polysomal mRNA fractions of hASC to study posttranscriptional regulation during the initial steps of adipogenesis. Results. We identified 3420 proteins out of 48,336 peptides, of which 92 proteins were exclusively identified in undifferentiated hASC and 53 proteins were exclusively found in 24 h-differentiated cells. Using a stringent criterion, we identified 33 differentially abundant proteins when comparing 24 h-differentiated and undifferentiated hASC (14 upregulated and 19 downregulated, respectively). Among the upregulated proteins, we shortlisted several adipogenesis-related proteins. A combined analysis of the proteome and the transcriptome allowed the identification of positive correlation coefficients between proteins and mRNAs. Conclusions. These results demonstrate a specific proteome profile related to adipogenesis at the beginning (24 hours) of the differentiation process in hASC, which advances the understanding of human adipogenesis and obesity. Adipogenic differentiation is finely regulated at the transcriptional, posttranscriptional, and posttranslational levels.

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Section: Discussionmentioning

confidence: 99%

Proteogenomic Analysis Reveals Proteins Involved in the First Step of Adipogenesis in Human Adipose-Derived Stem Cells

Bonilauri

Camillo-Andrade

Santos

et al. 2021

Stem Cells International

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“…This study further linked disrupted EC signaling to impaired liver development, hepatic differentiation, and proliferation ( 30 ). In contrast, zebrafish treated with AEA demonstrated enhancement of srebf1 expression known to promote hepatic lipid accumulation, lipotoxicity, and enhancement of insulin-like growth factors ( igf1 / igf2 ) known to promote adipocyte proliferation, differentiation, and deposition, suggesting that activation of the EC system may promote lipogenic processes ( 31 , 32 , 33 , 34 ).…”

mentioning

confidence: 99%

Vitamin D deficiency promotes accumulation of bioactive lipids and increased endocannabinoid tone in zebrafish

Knuth

Stutts

Ritter

et al. 2021

Journal of Lipid Research

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Circulating total IGF1 levels increased in mice of both sexes with HFD-induced weight gain, as in previous studies 75 , 76 ; however, no dietary changes in free IGF1, IGF2 or IGFBP2 levels were found here. Some studies report an increase 38 , 77 and others a reduction 78 in circulating IGF2 levels in patients with obesity, with these differences possibly being due to the degree and/or duration of obesity. IGFBP2, with reduced circulating levels in patients with obesity 34 , 38 , 79 and animal models of obesity 80 , is purported to be protective against obesity and diabetes onset 42 , 43 .…”

Section: Discussionmentioning

confidence: 99%

The metabolic effects of resumption of a high fat diet after weight loss are sex dependent in mice

Guerra-Cantera,

Frago,

Jiménez-Hernaiz

et al. 2023

Sci Rep

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Dietary restriction is a frequent strategy for weight loss, but adherence is difficult and returning to poor dietary habits can result in more weight gain than that previously lost. How weight loss due to unrestricted intake of a healthy diet affects the response to resumption of poor dietary habits is less studied. Moreover, whether this response differs between the sexes and if the insulin-like growth factor (IGF) system, sex dependent and involved in metabolic control, participates is unknown. Mice received rodent chow (6% Kcal from fat) or a high-fat diet (HFD, 62% Kcal from fat) for 4 months, chow for 3 months plus 1 month of HFD, or HFD for 2 months, chow for 1 month then HFD for 1 month. Males and females gained weight on HFD and lost weight when returned to chow at different rates (p < 0.001), but weight gain after resumption of HFD intake was not affected by previous weight loss in either sex. Glucose metabolism was more affected by HFD, as well as the re-exposure to HFD after weight loss, in males. This was associated with increases in hypothalamic mRNA levels of IGF2 (p < 0.01) and IGF binding protein (IGFBP) 2 (p < 0.05), factors involved in glucose metabolism, again only in males. Likewise, IGF2 increased IGFBP2 mRNA levels only in hypothalamic astrocytes from males (p < 0.05). In conclusion, the metabolic responses to dietary changes were less severe and more delayed in females and the IGF system might be involved in some of the sex specific observations.

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Insulin-like growth factor 2 promotes adipocyte proliferation, differentiation and lipid deposition in obese type 2 diabetes

Cited by 6 publications

References 31 publications

Proteogenomic Analysis Reveals Proteins Involved in the First Step of Adipogenesis in Human Adipose-Derived Stem Cells

Proteogenomic Analysis Reveals Proteins Involved in the First Step of Adipogenesis in Human Adipose-Derived Stem Cells

Vitamin D deficiency promotes accumulation of bioactive lipids and increased endocannabinoid tone in zebrafish

The metabolic effects of resumption of a high fat diet after weight loss are sex dependent in mice

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