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Sexual dimorphism in glucose and lipid metabolism

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The existence of sexual dimorphisms in whole body energy metabolism is evident from the apparent differences in the percentage of body fat between men and women. Even though women have more body fat than men, the female pear-shaped fat distribution does, relative to the visceral obesity typical of men, result ...

The existence of sexual dimorphisms in whole body energy metabolism is evident from the apparent differences in the percentage of body fat between men and women. Even though women have more body fat than men, the female pear-shaped fat distribution does, relative to the visceral obesity typical of men, result in protection against development of metabolic diseases such as insulin resistance, non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. The differences in body composition between men and women does not only apply to the distribution of white adipose tissue (WAT) but is also observed in ectopic fat accumulation such as in the liver and skeletal muscle, all central to the pathophysiology of development of metabolic diseases.

Numerous studies have demonstrated that some proteins involved in e.g. signaling pathways, enzymatic reactions and transport of metabolites are expressed in a sex specific manner. These differences in protein expression are also reflected in physiological measures such as women responding to fasting with higher levels of circulating free fatty acid and glycerol, but lower plasma glucose concentrations. Women also presents a less pro-atherogenic plasma lipid profile than men, with higher concentrations of high-density lipoprotein (HDL) cholesterol, and lower levels of low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol and total plasma triglyceride than men both in the fed and fasted state. These differences in lipid metabolism play a central role in the delayed development of cardiovascular disease observed in women when compared to men. However, intriguingly, women with diabetes are at greater risk for cardiovascular complications than their male counterparts.

Differences in life-style between men and women possibly can be account for some of the observed dissimilarities. However, the main contributor to the advantage of women seems to be the hormonal milieu. There are several ways that estrogens influences energy balance, and one of these is by acting on different hypothalamic regions of the central nervous system and thus affecting both food intake and energy expenditure. In addition, estrogen directly modulates the insulin sensitivity of peripheral tissues, leaving premenopausal women with a higher insulin sensitivity in WAT, liver and skeletal muscle than men as well as estrogen directly influences cardiovascular risk factors, such as inflammation, the coagulant system and vasodilatation. The understanding of the molecular mechanisms behind the influence of sex on the susceptibility to develop type 2 diabetes, NAFLD and cardiovascular disease would unravel novel insights into the pathophysiology of these metabolic diseases. This would also promote the discovery of novel targets for treatment as well as potential gender differences in effects and side effects in treatment will be revealed. Therefore the scope of this research topic is novel insights into pathways/proteins/metabolites that is expressed/regulated in a gender dependent manner as well as manuscripts that focuses on the molecular pathways that controls these differences are welcome. Studies ranging from the molecular and cellular level to the integrated organ and organism level are encouraged. The topic is open to original studies and theoretical approaches, description of novel methods, opinions and reviews.


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