Sex differences in metabolic homeostasis, diabetes, and obesity

Mauvais-Jarvis, Franck

doi:10.1186/s13293-015-0033-y

Cited by 459 publications

(438 citation statements)

References 82 publications

Supporting

Mentioning

410

Contrasting

Unclassified

Order By: Relevance

“…Female‐specific production of 17‐β estradiol contributes to sex differences in metabolism, supported by the observation that circulating 17‐β estradiol production declines during menopause, a fall associated with lower glucose homeostasis and elevated visceral adiposity (Mauvais‐Jarvis, 2015). However, other estrogens, and estrogenic actions outside of the classical ER receptors, are increasingly recognized to have potential health and anti‐aging benefits, which may mimic or operate outside of the effects of 17‐β estradiol on its best‐characterized receptors.…”

Section: Introductionmentioning

confidence: 98%

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

et al. 2018

View full text Add to dashboard Cite

SummaryLongevity in mammals is influenced by sex, and lifespan extension in response to anti‐aging interventions is often sex‐specific, although the mechanisms underlying these sexual dimorphisms are largely unknown. Treatment of mice with 17‐α estradiol (17aE2) results in sex‐specific lifespan extension, with an increase in median survival in males of 19% and no survival effect in females. Given the links between lifespan extension and metabolism, we performed untargeted metabolomics analysis of liver, skeletal muscle and plasma from male and female mice treated with 17aE2 for eight months. We find that 17aE2 generates distinct sex‐specific changes in the metabolomic profile of liver and plasma. In males, 17aE2 treatment raised the abundance of several amino acids in the liver, and this was further associated with elevations in metabolites involved in urea cycling, suggesting altered amino acid metabolism. In females, amino acids and urea cycling metabolites were unaffected by 17aE2. 17aE2 also results in male‐specific elevations in a second estrogenic steroid—estriol‐3‐sulfate—suggesting different metabolism of this drug in males and females. To understand the underlying endocrine causes for these sexual dimorphisms, we castrated males and ovariectomized females prior to 17aE2 treatment, and found that virtually all the male‐specific metabolite responses to 17aE2 are inhibited or reduced by male castration. These results suggest novel metabolic pathways linked to male‐specific lifespan extension and show that the male‐specific metabolomic response to 17aE2 depends on the production of testicular hormones in adult life.

show abstract

Section: Introductionmentioning

confidence: 98%

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Sexual dimorphism of the process is mostly driven by the genetic sex, the programming effect of testosterone in males during the perinatal period, and the role of sex hormones at puberty [2]. For example, experimental exposure of females to testosterone during the perinatal period (which occurs in males but not in females) induces male food behavior via the androgen receptors (ARs) and leptin-resistance through activation of the estrogen receptors (ERs), both concurring to obesity in adulthood [16].…”

Section: Energy Homeostasis Is a Physiological Function With Strong Smentioning

confidence: 99%

“…Although females have more subcutaneous adipose mass than males and males more muscle mass than women, fat subcutaneous distribution is not detrimental as compared to males which accumulate visceral fat upon body weight gain predisposing them to diabetes and cardiovascular diseases [2]. In addition, excess of estrogens such as during the estrous periods, during gestation and through pill consuming, results in insulin resistance favoring weight gain while estrogen deficiency such as during the menopausal transition also favors weight gain, accumulation of visceral fat and development of type 2 diabetes.…”

Section: Energy Homeostasis Is a Physiological Function With Strong Smentioning

confidence: 99%

“…Males had impaired cholesterol metabolism suggesting that the mixture could have impacted the estrogen/androgen balance as androgens regulate lipid accumulation and cholesterol metabolism in the male liver [31,32] and estrogens protect females from cardiovascular diseases [2]. Conversely, immature females with low levels of circulating estrogens showed alleviation of metabolic outcomes together with enhanced glucose tolerance, enhanced lean mass and muscle insulin sensitivity and reduced inflammation in the adipose tissue [33], all consistent with enhanced and benefitial estrogen signaling as shown in Table 1.…”

Section: Environmental Exposure To Endocrine Disruptors and Sex Dimormentioning

confidence: 99%

“…Notably, several compounds display estrogeno-mimetic activities and models of estrogen deficiency/excess in both humans and rodents, both in males and females, have well illustrated the importance of estrogens in regulating energy homeostasis and insulin sensitivity when estrogens stay within tight physiological concentrations. Indeed, energy homeostasis is largely dependent on sex-specific mechanisms regulating eating behavior, energy expenditure, fat distribution, insulin sensitivity and glucose tolerance [2]. Accordingly, it was anticipated that compounds with estrogenic, anti-estrogenic or anti-androgenic activities will act as metabolic disruptors and that the adverse effects may be sex-specific.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sex-specific metabolic alterations induced by environmental pollutants

Magueresse-Battistoni

Vidal

Naville

2018

Current Opinion in Toxicology

View full text Add to dashboard Cite

Conflicts of interest: noneFunding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 2 AbstractDiabetes and obesity are the biggest public health challenge and the current prevalence of these chronic diseases has reached epidemic proportions worldwide. Apart from genetic alterations and lifestyle, exposure to environmental chemicals has emerged as a new cause of metabolic diseases. Notably, several compounds that mimic or oppose hormone activity defined as endocrine disruptors (EDs), may exert metabolic disturbances through interfering with the regulatory roles of the sex steroids (among other hormones) in energy homeostasis.However, most studies to date have investigated the metabolic impact of EDs on males and there is a lack of information regarding the metabolic impact of endocrine disruptors in females. There is as well a paucity of data for both sexes related to the metabolic impact resulting from the exposure to a mixture of EDs which is a more realistic scenario than the exposure to chemicals individually. Hopefully, conducting studies on both sexes in situations of multi-exposure to chemicals will help at better understanding the sex-biased mechanisms linked to endocrine disruption that could be helpful to improve and personalize treatments of diseases for which obesity is a risk factor, such as the metabolic syndrome and the hormonodependent cancers. Bullet points:Energy homeostasis is a physiological function with strong sex-dimorphic outcomes Endocrine disruptors (EDs) are chemicals that interfere with any hormone action EDs may induce metabolic disturbances in a sex-specific wayThere is a lack of data on the metabolic impact of EDs in femalesThere is a lack of data on the metabolic impact of mixture of EDs in both sexes

show abstract

The Association of Metabolic Syndrome and Obesity With Clinical Hip Osteoarthritis in the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study Cohorts

Cheng

Strotmeyer

Kado

et al. 2023

ACR Open Rheumatology

View full text Add to dashboard Cite

Objective Metabolic dysregulation frequently co‐occurs with obesity, which has been shown to be a risk factor for lower extremity osteoarthritis (OA). We evaluated the association between metabolic syndrome (MetS), alone and in combination with obesity, and hip OA. Methods In two parallel cross‐sectional analyses, we studied 403 women from the Study of Osteoporotic Fractures (SOF) and 2354 men from the Osteoporotic Fractures in Men (MrOS) study. We used multivariable logistic regression to evaluate associations of obesity (body mass index ≥30 kg/m2) and/or MetS (three of five National Cholesterol Education Program Adult Treatment Panel III criteria) with clinical hip OA, defined as a modified Croft score of 2 or more or total hip replacement, and pain or limited range of motion. Our analysis adjusted for demographics. Results Approximately 3.5% of SOF women and 5.4% of MrOS men had clinical hip OA. Among women, obesity was not associated with hip OA, yet those with MetS had a 365% higher odds of hip OA (95% CI: 1.37‐15.83). Among men, those who had obesity had a 115% higher odds of hip OA (95% CI: 1.39‐3.32), yet MetS was not associated with hip OA. There was no interaction between MetS, obesity, and hip OA in either women or men. Conclusion In women, but not in men, MetS was associated with hip OA. In men, but not in women, obesity was associated with hip OA. These findings suggest that mechanical effects of obesity may predominate in the pathogenesis of hip OA in men, whereas metabolic effects predominate in women.

show abstract

Sex differences in metabolic homeostasis, diabetes, and obesity

Cited by 459 publications

References 82 publications

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice

Sex-specific metabolic alterations induced by environmental pollutants

The Association of Metabolic Syndrome and Obesity With Clinical Hip Osteoarthritis in the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study Cohorts

Contact Info

Product

Resources

About