Dynamics of human adipose lipid turnover in health and metabolic disease

Abstract

Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, lipid age was determined by measuring nuclear bomb test-derived 14C in adipocyte lipids. We report that during the average ten year life span of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate from fat tissue is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidemia, familial combined hyperlipidemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal play different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.

Semaphorin 3C is a novel adipokine linked to extracellular matrix composition

“…The observation that SEMA3C expression correlated significantly with adipocyte morphology (a measure that is independent of body fat mass as discussed [18]) demonstrates that there is a link between relative fat-cell size and SEMA3C levels. Fat-cell morphology is determined by adipocyte [18] and lipid turnover [44]. However, the transcriptional networks that regulate these processes have not yet been determined and their potential role in regulating SEMA3C requires further investigation.…”

The effect of inhibition of endoplasmic reticulum stress on lipolysis in white adipose tissue in a rat model of chronic kidney disease

“…Lipolysis in white adipose tissue, the cleavage of triglycerides and the release of fatty acids and glycerol play essential roles not only in lipid and energy homeostasis [26] but also in the development of lipotoxicity and fat redistribution [27,28] . Here, we have shown that lipolysis is enhanced in the visceral white adipose tissue in a rat model of CKD.…”

Understanding cancer stem cell heterogeneity and plasticity

“…At age 50, 55% of human cardiomyocytes remain from birth and over the first decade of life, cardiomyocytes often undergo a final round of DNA synthesis and nuclear division without cell division, resulting in ~25% of human cardiomyocytes being binucleated [19]. Similarly, the average lifespan of human adipocytes is ~10 years and the number of fat cells in adult humans remains quite constant with an annual turnover rate of only ~10% [20,21]. The post-mitotic nature of terminally differentiated cells would suggest that dedifferentiation, a process thought to be genetically regulated [22,23] in which a specialized cell takes on a more primitive state, although representing one potential aspect of plasticity in the stem cell progeny, may not take place prevalently under homeostatic conditions in adult mammalian organs ( Figure 3A).…”