Journal Article

Dynamics of human adipose lipid turnover in health and metabolic disease

Skurk, Thomas, Liebl, Jakob, Arner, Peter, Frayn, Keith N., Possnert, Göran, Eriksson, Mats, Spalding, Kirsty L., Buchholz, Bruce A., Arner, Erik, Salehpour, Mehran, Rydén, Mikael, Steier, Peter, Bernard, Samuel, Hauner, Hans

2011

Overview

Long-term lipid turnover in adipose tissue Lipid turnover is an important factor in determining how adipose tissue stores and releases energy in humans. By measuring carbon-14, derived from nuclear bomb tests, in the fat-cell lipids of a large cohort of individuals, Arner et al . estimate lipid turnover over a prolonged period in sickness and in health. The data show that during the ten-year lifespan of a typical human adipocyte, its triglyceride content is renewed six times. Unusual lipid turnover patterns correlate to conditions with disturbed lipid metabolism, suggesting it as a potential target for the treatment of metabolic disease. Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes 1 . Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo , here we determined lipid age by measuring 14 C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan 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 (lipolysis followed by oxidation) 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 dyslipidaemia, familial combined hyperlipidaemia. 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 have 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 dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/443/319 / 631/45/287 / 692/308 / 692/699/317 / Adipocytes - chemistry / Adipocytes - metabolism / Adipose tissue / Adipose Tissue - cytology / Adipose Tissue - metabolism / Adolescent / Adult / Aged / Aged, 80 and over / BASIC BIOLOGICAL SCIENCES / Biological and medical sciences / Carbon Radioisotopes - analysis / Care and treatment / Cell Size / Cellular Biology / Cellular Senescence / Child / Child, Preschool / Cohort Studies / DNA - chemistry / Dynamical Systems / Dyslipidemias - metabolism / Dyslipidemias - pathology / Fat cells / Health / Health aspects / Humanities and Social Sciences / Humans / Hyperlipidemia, Familial Combined - genetics / Hyperlipidemia, Familial Combined - metabolism / Hyperlipidemia, Familial Combined - pathology / letter / Life Sciences / Lipid Metabolism / Lipids / Lipolysis / Mathematics / Medical sciences / Metabolic diseases / Metabolic Diseases - metabolism / Metabolic disorders / Middle Aged / multidisciplinary / Nuclear Weapons / Nutrition / Obesity / Obesity - metabolism / Pathology / Physiological aspects / Prevention / Risk factors / Science / Science (multidisciplinary) / Subcutaneous Fat - metabolism / Time Factors / Triglycerides / Triglycerides - analysis / Triglycerides - metabolism / Young Adult