Estrogen Deficiency and the Origin of Obesity during Menopause

Abstract

Sex hormones strongly influence body fat distribution and adipocyte differentiation. Estrogens and testosterone differentially affect adipocyte physiology, but the importance of estrogens in the development of metabolic diseases during menopause is disputed. Estrogens and estrogen receptors regulate various aspects of glucose and lipid metabolism. Disturbances of this metabolic signal lead to the development of metabolic syndrome and a higher cardiovascular risk in women. The absence of estrogens is a clue factor in the onset of cardiovascular disease during the menopausal period, which is characterized by lipid profile variations and predominant abdominal fat accumulation. However, influence of the absence of these hormones and its relationship to higher obesity in women during menopause are not clear. This systematic review discusses of the role of estrogens and estrogen receptors in adipocyte differentiation, and its control by the central nervous systemn and the possible role of estrogen-like compounds and endocrine disruptors chemicals are discussed. Finally, the interaction between the decrease in estrogen secretion and the prevalence of obesity in menopausal women is examined. We will consider if the absence of estrogens have a significant effect of obesity in menopausal women.

Figure 1

Estrogen in the fat cell. (a) In brown adipocyte cell the ER alpha receptor can increase the expression of UCP1 by increasing PGC1alpha coactivator through AMPk and by a direct effect on the receptor coactivator. (b) In white adipocyte ER alpha receptor activation by estrogen reduces lipoprotein lipase and increases beta-adrenergic receptor activity. UCP1: uncoupling protein 1; PGC1alpha: peroxisome proliferative activated receptor gamma coactivator 1 alpha; ER: estrogen receptor; AMPk: AMP-activated protein kinase. LPL: lipoprotein lipase; β-AR: adrenergic receptor beta.

Figure 2

Estrogen hypothalamic control of obesity. ER alpha in the brain regulates body weight in both males and females ▸ ER alpha in female SF1 neurons regulates energy expenditure and fat distribution ▸ ER alpha in female POMC neurons regulates food intake. POMC: proopiomelanocortin; SF1: steroidogenic factor-1.

Figure 3

Estradiol availability affects the regulation of enzymes involved in tricarboxylic acid cycle activity. E2 enhances the glycolytic/pyruvate/acetyl-CoA pathway to generate electrons required for oxidative phosphorylation and ATP generation to sustain utilization of glucose as the primary fuel source.

Figure 4

Components with estrogens effects. Estrogen and some endocrine disruptors that have an estrogenic effect. DDT is a chemical fertilizer. Bisphenol A is an organic compound used to make polycarbonate polymers and epoxy resins; Genistein is an isoflavone found in a number of plants including soy. DDT: dichlorodiphenyltrichloroethane.