Sex hormone imbalances and adipose tissue dysfunction impacting on metabolic syndrome; a paradigm for the discovery of novel adipokines

Hui Zhang 1  and M. Ram Sairam 1
  • 1 Molecular Endocrinology Laboratory, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal H2W 1R7, Quebec, Canada
Hui Zhang and M. Ram Sairam


Sex hormone imbalance is causally related with visceral adipose tissue (AT) dysfunction and visceral obesity – an etiological component of metabolic syndrome (MetS), associated with high risk of both cardiovascular disease (CVD) and type 2 diabetes. In general, premenopausal women appear to be protected from CVD and the dramatic decline in sex steroid hormone occurring during menopausal transitions or other sex-related disorders influence the regional distribution, function, and metabolism of AT and increase the risk of CVD. Visceral AT dysfunction, manifesting as abnormality of fatty acid metabolism, increased oxidative stress, endothelial dysfunction, and excessive production of adipokines have been proposed in the pathogenesis of MetS. However, direct evidence of molecular mechanisms of depot-specific AT alterations, and dysfunction causally related to MetS is limited in studies on postmenopausal women due to difficulty in collecting discrete AT specimens at different ages and repeated sampling from different fat depots. This can be overcome using animal models that can mimic the cluster of pathology leading to MetS and help establish the molecular basis of links between loss of gonadal function on various AT depots and their contribution to MetS. Our group used sex hormone imbalance FSH receptor knock out (FORKO) female mice to recapitulate different aspects of the MetS and addressed the mechanism of visceral obesity related to MetS and discover two novel sex steroid hormone-regulated deep mesenteric estrogen-dependent adipose (MEDAs) genes. Taken together, such recent studies raise hopes for pharmacologic intervention strategies targeting sex steroid hormone signaling in AT to provide protection against AT dysfunction.

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Hormone Molecular Biology and Clinical Investigation is dedicated to the provision of data on molecular aspects of hormones in physiology and pathophysiology. The journal covers the treatment of diseases, such as endocrine cancers, renal and lymphoid carcinoma, hypertension, cardiovascular systems, osteoporosis, hormone deficiency in menopause and andropause, obesity, diabetes, brain and related diseases.