Adipose Tissue Dynamics: Cellular and Lipid Turnover in Health and Disease.

The alarming increase in obesity and its related metabolic health complications, such as type 2 diabetes, has evolved into a global pandemic. Obesity is mainly characterized by excessive accumulation of adipose tissue, primarily due to an imbalance between energy intake and expenditure. Prolonged positive energy balance leads to the expansion of existing adipocytes (hypertrophy) and/or an increase in preadipocyte and adipocyte number (hyperplasia) to accommodate excess energy intake. However, obesity is not solely defined by increases in adipocyte size and number. The turnover of adipose tissue cells also plays a crucial role in the development and progression of obesity. Cell turnover encompasses the processes of cell proliferation, differentiation, and apoptosis, which collectively regulate the overall cell population within adipose tissue. Lipid turnover represents another critical factor that influences how adipose tissue stores and releases energy. Our understanding of adipose tissue lipid turnover in humans remains limited due to the slow rate of turnover and methodological constraints. Nonetheless, disturbances in lipid metabolism are strongly associated with altered adipose tissue lipid turnover. In obesity, there is a decreased rate of triglyceride removal (lipolysis followed by oxidation), leading to the accumulation of triglycerides over time. This review provides a comprehensive summary of findings from both in vitro and in vivo methods used to study the turnover of adipose cells and lipids in metabolic health and disease. Understanding the mechanisms underlying cellular and lipid turnover in obesity is essential for developing strategies to mitigate the adverse effects of excess adiposity.

Childhood obesity: Implications on adipose tissue dynamics and metabolic health.

Obesity is the leading risk factor for the development of type 2 diabetes and cardiovascular diseases. Childhood obesity represents an alarming health challenge because children with obesity are prone to remain with obesity throughout their life and have an increased morbidity and mortality risk. The ability of adipose tissue to store lipids and expand in size during excessive calorie intake is its most remarkable characteristic. Cellular and lipid turnovers determine adipose tissue size and are closely related with metabolic status. The mechanisms through which adipose tissue expands and how this affects systemic metabolic homeostasis are still poorly characterized. Furthermore, the mechanism through which increased adiposity extends from childhood to adulthood and its implications in metabolic health are in most part, still unknown. More studies on adipose tissue development in healthy and children with obesity are urgently needed. In the present review, we summarize the dynamics of white adipose tissue, from developmental origins to the mechanisms that allows it to grow and expand throughout lifetime and during obesity in children and in different mouse models used to address this largely unknown field. Specially, highlighting the role that excessive adiposity during the early life has on future's adipose tissue dynamics and individual's health.

Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.

Postnatal overfeeding increases the risk of chronic diseases later in life, including obesity, insulin resistance, hepatic steatosis, and type 2 diabetes. Epigenetic mechanisms might underlie the long-lasting effects associated with early nutrition. Here we aimed to explore the molecular pathways involved in early development of insulin resistance and hepatic steatosis, and we examined the potential contribution of DNA methylation and histone modifications to long-term programming of metabolic disease. We used a well-characterized mouse model of neonatal overfeeding and early adiposity by litter size reduction. Neonatal overfeeding led to hepatic insulin resistance very early in life that persisted throughout adulthood despite normalizing food intake. Up-regulation of monoacylglycerol O-acyltransferase ( Mogat) 1 conceivably mediates hepatic steatosis and insulin resistance through increasing intracellular diacylglycerol content. Early and sustained deregulation of Mogat1 was associated with a combination of histone modifications that might favor Mogat1 expression. In sum, postnatal overfeeding causes extremely rapid derangements of hepatic insulin sensitivity that remain relatively stable until adulthood. Epigenetic mechanisms, particularly histone modifications, could contribute to such long-lasting effects. Our data suggest that targeting hepatic monoacylglycerol acyltransferase activity during early life might provide a novel strategy to improve hepatic insulin sensitivity and prevent late-onset insulin resistance and fatty liver disease.-Ramon-Krauel, M., Pentinat, T., Bloks, V. W., Cebrià, J., Ribo, S., Pérez-Wienese, R., Vilà, M., Palacios-Marin, I., Fernández-Pérez, A., Vallejo, M., Téllez, N., Rodríguez, M. À., Yanes, O., Lerin, C., Díaz, R., Plosch, T., Tietge, U. J. F., Jimenez-Chillaron, J. C. Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.