Question

why it makes metabolic sense for adipocytes release leptin in response to short chain fatty acids

Answer 1

Leptin is an adipose-derived hormone that regulates a wide variety of physiological processes, including feeding behavior, metabolic rate, sympathetic nerve activity, reproduction, and immune response. Leptin is a circulating hormone secreted primarily by white adipose tissue, an organ that functions not only in energy storage but also as an important site for the production of endocrine factors Among the above regulators, catecholamines, adenosine, and endothelins all act by means of cognate G protein-coupled receptors (GPCRs) expressed in adipocytes. Adipocytes express high levels of β-adrenergic receptors, and activation of the Gs pathway by the β-adrenergic agonist isoproterenol increases intracellular cAMP levels. Adipocytes produce adenosine, which acts as an autocrine factor through the Gi-coupled A1 receptor present in these cells . Addition of adenosine deaminase to the medium depletes adenosine released by adipose tissue in primary culture. The basal level of leptin production in primary cultures of native adipose tissue is reduced in the presence of 10 units per ml adenosine deaminase, in accordance with a previous report showing that adenosine is an activator of leptin production . However, rather than being diminished, the response of adipose tissue to propionic acid is further enhanced by adenosine deaminase treatment, implying that the Gi pathway is desensitized by the constant presence of autocrine adenosine, whereas depletion of adenosine resensitizes this pathway on which propionate/GPR41 works.