Differential expression of immunoregulatory cytokines in adipose tissue and liver in response to high fat and high sugar diets in female mice

A comprehensive understanding of how dietary components impact immunoregulatory gene expression in adipose tissue (AT) and liver, and their respective contributions to metabolic health in mice, remains limited. The current study aimed to investigate the metabolic consequences of a high-sucrose diet (HSD) and a high-fat diet (HFD) in female mice with a focus on differential lipid- and sucrose-induced changes in immunoregulatory gene expression in AT and liver. Female C57BL/6 J mice were fed a purified and macronutrient matched high fat, high sugar, or control diets for 12 weeks. Mice were extensively phenotyped, including glucose and insulin tolerance tests, adipose and liver gene and protein expression analysis by qPCR and Western blot, tissue lipid analyses, as well as histological analyses. Compared to the control diet, HSD- and HFD-fed mice had significantly higher body weights, with pronounced obesity along with glucose intolerance and insulin resistance only in HFD-fed mice. HSD-fed mice exhibited an intermediate phenotype, with mild metabolic deterioration at the end of the study. AT lipid composition was significantly altered by both diets, and inflammatory gene expression was only significantly induced in HFD-fed mice. In the liver however, histological analysis revealed that both HSD- and HFD-fed mice had pronounced ectopic lipid deposition indicating hepatic steatosis, but more pronounced in HSD-fed mice. This was in line with significant induction of pro-inflammatory gene expression specifically in livers of HSD-fed mice. Overall, our findings suggest that HFD consumption in female mice induces more profound inflammation in AT with pronounced deterioration of metabolic health, whereas HSD induced more pronounced hepatic steatosis and inflammation without yet affecting glucose metabolism

Expression of the Adipocyte Progenitor Markers MSCA1 and CD36 is Associated With Adipose Tissue Function in Children

International audienceContext: MSCA1 (mesenchymal stem cell antigen 1) and CD36 (cluster of differentiation 36) have been described as novel adipocyte progenitor markers in adults with a potential relevance for obesity and adipocyte progenitor function. Objective: With the early manifestation of obesity in children and formation of adipose tissue (AT) dysfunction, children provide the opportunity to characterize the function of MSCA1 and CD36 during physiological AT accumulation and with obesity and related disease. Methods: We investigated MSCA1 and CD36 expression in adipocytes and stroma vascular fraction (SVF) cells from 133 children of the Leipzig AT Childhood cohort with regard to AT accumulation and biology. In a subsample we analyzed how MSCA1 and CD36 expression is related to adipose progenitor capacities in vitro (ie, proliferation, differentiation and mitochondrial function). Results: Both MSCA1 and CD36 are differentially expressed in adipocytes and SVF cells of children. MSCA1 expression is positively correlated to obesity-associated AT dysfunction (ie, adipocyte hypertrophy and serum high-sensitivity C-reactive protein), and high SVF MSCA1 expression is associated with increased mitochondrial respiration in vitro. CD36 expression is not associated with AT dysfunction but SVF CD36 expression is downregulated in children with overweight and obesity and shows a positive association with the differentiation capacity of SVF cells ex vivo and in vitro

Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells

ABSTRACTS-adenosyl-homocysteine-hydrolase (AHCY) plays an important role in the methionine cycle regulating cellular methylation levels. AHCY has been reported to influence proliferation and differentiation processes in different cell types, e.g. in cancer cells and mouse embryonic stem cells. In the development of adipose tissue, both the proliferation and differentiation of adipocyte progenitor cells (APCs) are important processes, which in the context of obesity are often dysregulated. To assess whether AHCY might also be involved in cell proliferation and differentiation of APCs, we investigated the effect of reduced AHCY activity on human and mouse APCs in vitro. We show that the inhibition of AHCY using adenosine dialdehyde (AdOx) and the knockdown of AHCY using gene-specific siRNAs reduced APC proliferation and number. Inhibition of AHCY further reduced APC differentiation into mature adipocytes and the expression of adipogenic differentiation markers. Global DNA methylation profiling in human APCs revealed that inhibition of AHCY is associated with alterations in CpG methylation levels of genes involved in fat cell differentiation and pathways related to cellular growth. Our findings suggest that AHCY is necessary for the maintenance of APC proliferation and differentiation and inhibition of AHCY alters DNA methylation processes leading to a dysregulation of the expression of genes involved in the regulation of these processes