Appetite and energy balance signals from adipocytes

Abstract

Interest in the biology of white adipose tissue has risen markedly with the recent surge in obesity and its associated disorders. The tissue is no longer viewed simply as a vehicle for lipid storage; instead, it is recognized as a major endocrine and secretory organ. White adipocytes release a multiplicity of protein hormones, signals and factors, termed adipokines, with an extensive range of physiological actions. Foremost among these various adipokines is the cytokine-like hormone, leptin, which is synthesized predominantly in white fat. Leptin plays a critical role in the control of appetite and energy balance, with mutations in the genes encoding the hormone or its receptor leading to profound obesity in both rodents and man. Leptin regulates appetite primarily through an interaction with hypothalamic neuroendocrine pathways, inhibiting orexigenic peptides such as neuropeptide Y and orexin A, and stimulating anorexigenic peptides such as proopiomelanocortin. White fat also secretes several putative appetite-related adipokines, which include interleukin-6 and adiponectin, but whether these are indeed significant signals in the regulation of food intake has not been established. Through leptin and the other adipokines it is evident that adipose tissue communicates extensively with other organs and plays a pervasive role in metabolic homeostasis.

Figure 1

Histological section of white adipose tissue illustrating, at the level of light microscopy, the apparent simplicity of the tissue. A haematoxylin–eosin stained section of epididymal adipose tissue from a NMRI mouse is shown.

Figure 2

Appetite suppressing effects of leptin. The figure illustrates the powerful inhibitory effect of leptin on food intake in ob/ob mice, which lack the functional hormone. Mice were injected with vehicle from days −4 to 0 and then with recombinant leptin (1.25 μg g⁻¹ body wt, twice daily) from days 0 to 7; they were then returned to vehicle injections. Adapted from Mercer et al. (1997).

Figure 3

Schematic view of the integrated signalling effect of leptin on appetite through the central hypothalamic neuroendocrine pathways. AgRP, agouti-related peptide; CART, cocaine- and amphetamine-regulated transcript; CRH, corticotrophin releasing hormone; MCH, melanin concentrating hormone; NPY, neuropeptide Y; POMC, pro-opiomelanocortin.

Figure 4

Leptin and putative appetite signals from white adipose tissue. IL, interleukin; TNFα, tumour necrosis factor-α.