Lipogenesis in Adipose Tissue

Abstract

The regulation of fatty acid synthesis in adipose tissue has been studied in vitro using the paired epididymal fat pads of the rat. Conditions which impair the utilization of glucose in this tissue, such as starvation or the induction of alloxan diabetes, virtually abolish fatty acid synthesis in adipose tissue. Insulin in vitro stimulates fatty acid synthesis from glucose in tissue from fed normal animals, and restores lipogenesis in adipose tissue fronm starved rats or rats with alloxan diabetes. Insulin also stimulates the incorporation of carbon from acetate, acetaldehyde, malonate and pyruvate into fatty acid but only in the presence of glucose. The effects of insulin on fatty acid synthesis from these four substrates thus appears to be secondary to its effects on carbohydrate metabolism in adipose tissue. The Embden-Meyerhof and phosphogluconate oxidative pathways are operative in adipose tissue, and evidence for the presence of the uronic acid pathway is presented. The phosphogluconate oxidative pathway, an important source of TPNH which is required for fatty acid synthesis, participates in the increased oxidation of glucose to CO₂ stimulated by insulin or ovine prolactin in vitro. This increased utilization of glucose is accompanied by increased fatty acid synthesis from glucose, and stimulates lipogenesis from acetate and pyruvate carbon in this tissue. The phosphogluconate oxidative pathway does not participate to the same extent in the increased production of CO₂ from glucose which follows the addition of bovine growth hormone in vitro. Growth hormone does not increase the incorporation of glucose carbon into long chain fatty acid, nor does it stimulate lipogenesis from acetate or pyruvate in the presence or absence of glucose. Evidence is presented which suggests that hormonal regulation of fatty acid synthesis in adipose tissue might be achieved not only by the control of glucose uptake, but also by alterations in the specific pathways of glucose metabolism operative at any given time.