Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity

Abstract

The aim of this review is to explore the dysregulation of adrenocortical secretions as a major contributor in the development of obesity and insulin resistance. Disturbance of adipose tissue physiology is one of the primary events in the development of pathologies associated with the metabolic syndrome, such as obesity and type 2 diabetes. Several studies indicate that alterations in metabolism of glucocorticoids (GC) and androgens, as well as aldosterone in excess, are involved in the emergence of metabolic syndrome. Cross talk among adipose tissue, the hypothalamo-pituitary complex, and adrenal gland activity plays a major role in the control of food intake, glucose metabolism, lipid storage, and energy balance. Perturbation of this cross talk induces alterations in the regulatory mechanisms of adrenocortical steroid synthesis, secretion, degradation, and/or recycling, at the level of the zonae glomerulosa (aldosterone), fasciculata (GC and GC metabolites), and reticularis (androgens and androgen precursors DHEA and DHEAS). As a whole, these adrenocortical perturbations contribute to the development of metabolic syndrome at both the paracrine and systemic level by favoring the physiological dysregulation of organs responsive to aldosterone, GC, and/or androgens, including adipose tissue. adrenal gland; adipocytes; angiotensin II; adrenocorticotropic hormone; adrenal steroids INSULIN RESISTANCE (IR), which is characterized by an insufficiency in insulin action, is associated with pathologies related to the metabolic syndrome, such as central obesity, hypertension, and dyslipidimia, and leads to increased risk of type 2 diabetes and cardiovascular diseases. Common forms of obesity and type 2 diabetes are polygenic diseases, resulting from complex interactions between genetic predispositions and environmental factors (18, 42), with particular importance of dietary fat intake (114,146). Current data converge to indicate that dysregulation in adipose tissue physiology is one of the primary events in the development of insulin resistance (52, 109, 111), although other insulin-and glucocorticoid-responsive organs such as skeletal muscles and liver may also play a primary role (144, 168). Several publications and reviews also point to glucocorticoids (GC) (151,190) and the renin-angiotensin system (RAS) as key players in controlling adipose tissue physiology (187). However, several reports indicate cross-talk relationships among the hypothalamo-pituitary-adrenal (HPA) axis, the melanocortin pathways, and the adipose tissue. Combination of certain gene variants with environmental factors, such as overheating, sedentarity, and chronic stress, appears to alter this cross talk, hence inducing perturbations in the regulatory mechanisms of adrenocortical steroid synthesis, secretion, degradation, and/or recycling. The aim of the present review is to explore the dysregulation of adrenocortical secretions as a major contributor in the development of obesity and insulin resistance. Structure and Functions of the Adrenal Cortex...

Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

“…Its role is not yet clearly defined, since it does not modify proliferation or protein synthesis in isolated cells (Otis et al 2005). However, several recent data have suggested that AT 2 R may ensure a protective role not only in the cardiovascular and renal systems (Carey & Padia 2008, Siragy 2009), but also in metabolic homeostasis, brain disorders and even in cancer (for reviews, see Henriksen (2007), Roberge et al (2007), Horiuchi et al (2010) and Steckelings et al (2010)). The change in protein levels of AT 1 R and AT 2 R in IUGR males in the present study led to a decrease in AT 1 R to AT 2 R ratio, which may have contributed to the observed reduction in aldosterone synthesis.…”

Association of plasma aldosterone with the metabolic syndrome in two German populations

“…Human adipocytes produce mineralocorticoid-releasing factors that stimulate aldosterone secretion, which in turn promotes adipogenesis (11,13,14). Furthermore, epidemiological studies demonstrate that high plasma aldosterone concentrations (PAC) are associated with impaired insulin metabolic signaling, impaired pancreatic b-cell function, and insulin resistance (15,16). In crosssectional analyses, associations of aldosterone with MetS were demonstrated (9,17).…”

Circadian Rhythm Gene Period 3 Is an Inhibitor of the Adipocyte Cell Fate

“…Glucocorticoids play a critical role in inducing the adipocyte cell fate and differentiation both in vivo and ex vivo (1)(2)(3). This regulatory process may be relevant to normal physiology and to disease states, as patients exposed chronically to excess glucocorticoids develop increased adiposity (4).…”