Molecular Insulin Actions Are Sexually Dimorphic in Lipid Metabolism

Abstract

The increment in energy-dense food and low physical activity has contributed to the current obesity pandemic, which is more prevalent in women than in men. Insulin is an anabolic hormone that regulates the metabolism of lipids, carbohydrates, and proteins in adipose tissue, liver, and skeletal muscle. During obesity, nutrient storage capacity is dysregulated due to a reduced insulin action on its target organs, producing insulin resistance, an early marker of metabolic dysfunction. Insulin resistance in adipose tissue is central in metabolic diseases due to the critical role that this tissue plays in energy homeostasis. We focused on sexual dimorphism on the molecular mechanisms of insulin actions and their relationship with the physiology and pathophysiology of adipose tissue. Until recently, most of the physiological and pharmacological studies were done in males without considering sexual dimorphism, which is relevant. There is ample clinical and epidemiological evidence of its contribution to the establishment and progression of metabolic diseases. Sexual dimorphism is a critical and often overlooked factor that should be considered in design of sex-targeted therapeutic strategies and public health policies to address obesity and diabetes.

The Effect of Sex and Obesity on the Gene Expression of Lipid Flippases in Adipose Tissue

“…The effects of obesity on ATP8A1 and ATP8B1 gene expression levels in VAT were sex-dependent, according to which higher effects were observed in men. Sex influences adipose tissue distribution but also influences adipose tissue function and metabolism [31], and major sex differences are observed in visceral adiposity before menopause [32]. In the same direction as our results, it has previously been reported that the lipid composition of the plasma membrane can be altered in a sex-specific manner [33].…”

“…In the present study, the expression of both P4-ATPases showed strong positive correlations with insulin and HOMA-IR in men but not in women. Adipose tissue plays a central role in modulating lipid metabolism, insulin sensitivity, and glucose homeostasis, and differences between males and females have been described in these actions [31], influencing their predisposition to diabetes and associated metabolic disorders [35]. Our results might be a consequence of the pathological distribution of fat in men, who accumulate more fat in visceral adipose tissue, providing evidence that fat distribution deserves more attention as a predictor of the comorbidities than it has been given [32].…”

Association of Dyslipidemia and Type-I Diabetes Mellitus Among Children Up to 16 Years of Age

“…Diabetes mellitus is a collection of carbohydrate metabolism disorders that have the common symptom of chronic hyperglycemia caused by production of insulin, insulin action. Insulin is a critical anabolic hormone that causes a variety of metabolic irregularities in proteins, lipids & carbs 11,12 . Reduced levels of high-density lipoprotein cholesterol & increase levels of low-density lipoprotein cholesterol or tri-glycerides explain diabetic dyslipidemia 13,14 .…”

Altered Adipokine Expression in Tumor Microenvironment Promotes Development of Triple Negative Breast Cancer

“…Although the role of excess fat accumulation in breast cancer pathogenesis is not fully understood, recent evidence underlines the role of hormonal alterations, insulin resistance, and deregulated secretion of adipose cytokines (adipokines) in obese, particularly post-menopausal, women with breast cancer [ 46 ]. It is well known that adipose tissue exerts highly complex endocrine activities and regulates the production of bioactive sex hormones, which increase breast cancer risk.…”