Triacylglycerols represent the largest energy reservoir of the body. The primary fat storage organ is white adipose tissue (WAT), which grows in response to excess energy intake, eventually leading to obesity, and shrinks in response to starvation. In addition to its function as an energy storage organ, the finely tuned regulation of triacylglycerol synthesis and degradation in WAT is required for control of circulating lipid levels. Defective WAT function may result in dyslipidaemia and fatty acid overload of non-adipose tissues, inducing ectopic triacylglycerol deposition, which is associated with insulin resistance, inflammation and impaired metabolic function of insulin-sensitive tissues [1]. This can occur in obese individuals when the storage capacity of adipose tissue is exceeded and in patients with loss-of-function mutations in genes regulating lipid storage, eg mutations in the gene encoding lipid droplet protein perilipin 1, which limits the access of lipases to fat stores, leading to lipodystrophy and severe insulin resistance [2]. Thus, efficient fatty acid storage in the form of inert triacylglycerol can be considered as a protective mechanism counteracting dyslipidaemia and metabolic disease.

In the current issue of Diabetologia, El-Assaad et al [3] describe the phenotype of mice lacking G0s2, the protein product of which (G0/G1 switch protein 2, G0S2) functions as a lipolysis inhibitor and consequently increases fat storage. Mechanistically, G0S2 acts by inhibiting adipose triglyceride lipase (ATGL) activity, which is required for efficient mobilisation of triacylglycerol stores [4]. ATGL-deficient mice are obese and also accumulate triacylglycerols in nonadipose tissues, including liver and muscle. These mice exhibit strongly reduced lipolysis, causing a shift from fatty acid to glucose oxidation, which is associated with improved glucose tolerance and insulin sensitivity, as well as protection against high-fat diet (HFD)-induced insulin resistance [5–7]. Considering triacylglycerol storage as a protective mechanism, one would expect G0S2-mediated inhibition of lipolysis to protect against insulin resistance. In line with this expectation, adipocyte-specific overexpression of G0s2 reduces lipolysis and increases fat mass. Despite increased obesity, these transgenic mice display decreased plasma fatty acid, triacylglycerol and insulin levels, as well as improved glucose and insulin tolerance [8]. These observations closely resemble the phenotype of mice lacking ATGL [5–7]. Based on observations in mice overexpressing G0s2 in adipose tissue, one would expect G0S2 deficiency to cause fatty acid overload, dyslipidaemia, and insulin resistance. In contrast to these expectations, El-Assaad et al [3] demonstrate that a lack of G0S2 affords protection against obesity and insulin resistance in HFD-fed mice. This was explained by increased β-oxidation and mitochondrial uncoupling, leading to in-