Final Report Summary - HUFATREG (Adipose tissue mass regulation in lean and obese individuals) My ERC HUFATREG project aimed to determine fat cell and lipid turnover dynamics in adult human adipose depots. Factors that may affect turnover dynamics, such as person BMI, adipose depot (visceral versus subcutaneous), fat cell size and weight gain/loss were also investigated. Results from the fat cell turnover projects are still ongoing, along with studies into adipocyte ploidy and nuclear responses to obesity. Most lipid studies have been completed and are summarized below.Excess triglycerides (TGs) are either stored in adipose tissue, or burned to meet the body’s energy demands through a process known as lipolysis. Although it has been proposed that the balance between TG storage and lipolysis is dysregulated in obesity, studies that quantify and compare lipid turnover in obese versus non-obese humans have been lacking. We used carbon dating to calculate the age of TGs within adipocytes, by taking advantage of atmospheric 14C released during above-ground nuclear testing that took place between 1955 and 1963. These results indicated that adipocytes in healthy individuals live for just under 10 years, during which their TG content is replaced approximately six times. In obese individuals, lipid turnover was found to be decreased and the rate of storage increased, causing accumulation of adipose tissue. In contrast, patients with familial combined hyperlipidaemia had low rates of both lipid storage and turnover, an imbalance that likely contributes to the increased circulating levels of TGs that are characteristic of this disease (Arner et al., 2011, Nature). Follow-up studies looking at lipid turnover in visceral and subcutaneous tissue show that excess WAT results in depot-specific differences in lipid turnover, with an increased turnover in visceral WAT and/or decreased turnover in subcutaneous WAT (Spalding et al., 2017, Nature Communications). These differences in lipid turnover between visceral and subcutaneous fat depots may result in the metabolic complications of overweight or obesity. Targeting mechanisms of TG turnover might therefore be a promising therapeutic strategy to combat metabolic diseases.