Adiponectin is an adipocyte
hormone that links visceral adiposity with
insulin resistance and
atherosclerosis. It is unique among adipocyte-derived
hormones in that its circulating concentrations are inversely proportional to adiposity, and low
adiponectin concentrations predict the development of
type 2 diabetes and
cardiovascular disease. Consequently, in the decade since its discovery,
adiponectin has generated immense interest as a potential therapeutic target for the
metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating
adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma
adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that
adiponectin production may be determined primarily by adipocyte size and
insulin sensitivity, with larger,
insulin-resistant adipocytes producing less
adiponectin. While
adiponectin concentrations are unchanged after meal ingestion, they are increased by significant
weight loss, such as after
bariatric surgery. In addition,
adiponectin production is inhibited by a number of
hormones, including
testosterone,
prolactin,
glucocorticoids and
growth hormone, and by
inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating
adiponectin concentrations. Dietary
fatty acid composition in rodents influences
adiponectin production via
ligand-activated
nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to
PPAR agonists (such as
thiazolidinediones and
fibrates), a number of pharmacological agents (
angiotensin receptor type 1 blockers,
ACE inhibitors, and
cannabinoid receptor antagonists) used in treatment of the
metabolic syndrome also increase
adiponectin concentrations in humans.