Serum Adiponectin Levels Are Inversely Associated with Overall and Central Fat Distribution but Are Not Directly Regulated by Acute Fasting or Leptin Administration in Humans: Cross-Sectional and Interventional Studies

Abstract

Adiponectin is an adipocyte-secreted protein that circulates in high concentrations in the serum and acts to increase insulin sensitivity. Previous studies have shown that serum adiponectin is inversely associated with fat mass and insulin resistance in humans and that acute fasting decreases adipose tissue adiponectin mRNA expression in rodents. Whether acute energy deprivation, body fat distribution, or serum hormone levels are associated with circulating adiponectin in humans remains largely unknown. To identify predictors of serum adiponectin levels, we evaluated the association of adiponectin with several anthropometric, metabolic, and hormonal variables in a cross-sectional study of 121 women without a known history of diabetes. We also performed interventional studies to assess whether fasting for 48 h and/or leptin administration regulates serum adiponectin in healthy men and women. Our cross-sectional study shows that, in addition to overall obesity, central fat distribution is an independent negative predictor of serum adiponectin and suggests that adiponectin may represent a link between central obesity and insulin resistance. In addition, estradiol is negatively and independently associated with adiponectin, whereas there is no association between serum adiponectin and leptin, cortisol, or free testosterone levels. Our interventional studies demonstrate that neither fasting for 48 h, resulting in a low leptin state, nor leptin administration at physiological or pharmacological doses alters serum adiponectin levels. Further studies are needed to fully elucidate the physiology of adiponectin in humans and its role in the pathogenesis of insulin-resistant states.

Maternal serum adiponectin levels during human pregnancy

“…Adiponectin expression and secretion have been shown to be subjected to regulation by numerous factors, some of which are possibly affected by the unique hormonal milieu of pregnancy. This hypothesis is supported by studies in mice, which suggest that estrogen, 19 prolactin 19 and testosterone 20 (all increased in normal human pregnancy) may affect adiponectin levels.…”

Adiponectin in relation to childhood myeloblastic leukaemia

“…Adiponectin acts principally as an insulin sensitiser; it is inversely associated with parameters of adult obesity and has anti-inflammatory and antiatherogenic effects Ouchi et al, 1999;Yokota et al, 2000;Ouchi et al, 2001;Motoshima et al, 2002;Cnop et al, 2003;Gavrila et al, 2003). Four epidemiological studies on adiponectin in relation to cancer have been undertaken among adults and all four have pointed to inverse associations of the hormone with breast cancer (Miyoshi et al 2003;Mantzoros et al 2004b) and endometrial cancer (Petridou et al, 2003;Dal Maso et al, 2004), notably with the postmenopausal forms of the two diseases.…”

“…Although adiponectin has generally been considered as a hormone-modulating insulin resistance-related phenomenon in adult life Stefan et al, 2002;Cnop et al, 2003;Gavrila et al, 2003) the very high levels of this hormone in early life (Mantzoros et al, 2004a) suggest an important role of adiponectin during this period as well. Our in vivo data in combination to the experimental findings by Yokota et al suggest that adiponectin may have a specific role in leukaemia which needs to be explored further in the future.…”

Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones

“…In contrast to most adipocyte hormones, adiponectin levels are lower in obese individuals and increase with weight loss. 2 Adiponectin is inversely related to both overall and intra-abdominal fat, 3 but is primarily produced by visceral adipose tissue. 4,5 Low levels of adiponectin have been implicated in the development of a number of obesityrelated conditions, including dyslipidemia, insulin resistance, type 2 diabetes and atherosclerotic heart disease.…”