The review discusses the hypothesis that a major function of insulin is to stimulate triglyceride accumulation in adipose tissue and glycogen synthesis in the liver and muscles. Malfunction of insulin decreases triglyceride storage in adipose tissue, while its extreme activation induces obesity. In either case, low-molecular-weight lipid metabolites, such as oxybutyrates, ketobutyrates, ketone bodies, etc., increase in content in peripheral tissues and are utilized as a preferable substrate in energy production, thus reducing the glucose uptake in cells. Leptin inhibits the lipogenic function of insulin and prevents lipid accumulation, while leptin deficiency or a decrease in leptin activity increases the lipid production and induces obesity. Lipodystrophy decreases leptin secretion by adipocytes and facilitates the lipogenic effect of insulin, but insulin does not stimulate the triglyceride accumulation in adipose tissue in the absence of subcutaneous fat. Lipid metabolites accumulate in peripheral organs and induce lipoatrophic diabetes mellitus. The hypothesis of the alternative mechanisms of insulin functioning is consented with the data obtained in mice with a targeted knockout of the insulin receptor gene in individual organs (muscles, adipose tissue, etc.) and transgenic animals with restored expression of the gene.