Study: Sex hormones, intestinal inflammation, and the gut microbiome: Major influencers of the sexual dimorphisms in obesity. Image Credit: SHISANUPONG1986/Shutterstock

Sexual dimorphisms in the epidemiology and pathophysiology of obesity

In a recent study published in Frontiers of Immunologyresearchers reviewed sexual dimorphisms in obesity.

Study: Sex hormones, intestinal inflammation and the gut microbiome: Major influences on sexual dimorphisms in obesity. Image credit: SHISANUPONG1986/Shutterstock

Background

Obesity, the accumulation of excess body fat, is associated with a higher risk of health problems such as diabetes, cardiovascular disease (CVD), and stroke. The prevalence of obesity has tripled over the past four decades and affects approximately 30% of adults worldwide. Notably, there are sexual dimorphisms in the pathophysiology and epidemiology of obesity.

Women are generally better protected from obesity than men, which has been attributed to several biological processes such as the gut immune system, gut microbiome, sex hormones/chromosomes, and fat distribution effects. In this review, researchers summarize the evidence for sexual dimorphisms and discuss the interplay between the gut microbiome, gut inflammation, and sex hormones.

Sexual dimorphisms in the distribution of adipose tissue, sex chromosomes and hormones

Historically, women have been underrepresented in preclinical research and clinical trials. This was partly due to the misconception that women and men were the same. That men and women are unique at the cellular level is now evident. Although slightly more prevalent in women than men, women are protected from the metabolic disturbances and consequences associated with disease progression in obesity.

Animal studies have shown that male rodents are prone to early onset and higher degrees of obesity than their female counterparts. Interestingly, older females or ovariectomized animals are less protected than younger animals with intact ovaries. This correlates with the epidemiology of obesity in humans, where postmenopausal men and women are at the highest risk of obesity complications, supporting that sex hormones (in premenopausal women) protect against obesity.

The distribution of adipose tissue differs between men and women. Women have more subcutaneous fat predominantly in the gluteofemoral region, while men primarily accumulate visceral fat in the abdominal region. Higher visceral adiposity in men impairs the secretion of pro-inflammatory molecules into the systemic circulation, creating a chain effect that significantly increases the risk of cardiovascular events.

Sex chromosomes are major contributors to sexual dimorphisms in adipose tissue distribution. In a mouse model, gonadectomized female and male mice carrying the XX chromosome complement had worse obesity outcomes than gonadectomized mice with XY chromosome complements.

Furthermore, gonadectomized mice with XO and XXY complements revealed that the differences between XY and XX mice were due to an additional X chromosome. Therefore, the X chromosome may be an important factor, in addition to sex hormones/gonads, for sexual dimorphism in obesity.

Changes in the gut microbiome in obesity

In addition, gender differences in obesity have been partially attributed to intersex dimorphism in gut microbiota. A diet high in bad fats and low in fiber can alter the microbial population within 24 hours. Dysbiosis occurs as a result of a poor diet and can be identified by the loss of beneficial bacteria and the increased presence of harmful bacteria.

Beneficial bacteria such as Bifidobacterium members and Akkermansie you’re alive negatively correlated with obesity, while harmful bacteria such as members of the Fusobacterium, Bilophila and Desulfovibrio gender is positively correlated with obesity. It is well known that sex steroid hormones control sexual dimorphism in males and females.

An observational study suggests that sex hormones influence gut microflora. Elevated hormone levels were associated with greater diversity of gut microbes compared to those with lower hormone levels in both sexes. Estradiol is used in hormone therapies to treat loss of ovarian estrogen, typically in menopausal women.

In mice, females fed a high-fat diet and treated with estradiol were protected from cardiometabolic disease compared to untreated mice. In addition, estradiol affects the composition of the gut microbiome by slowing the increase Firmicutes: Bacteroidetes ratio (an increased ratio is typically seen in obesity).

Gender differences in intestinal inflammation

Low-grade systemic inflammation is common in obesity. Many obesity studies have focused on visceral adipose tissue as causing inflammation. Nevertheless, intestinal inflammation occurs before obese characteristics and adipose tissue inflammation. This is particularly significant because a significant proportion of systemic innate and adaptive immune cells reside in the intestinal tract.

Intestinal microflora also affects intestinal immunity. Because of their proximity, the interplay between the gut immune system and gut microflora is known to evolve and shape each other. This is accentuated in germ-free mice, which lack gut microbes and consequently have poorly developed immune cell populations and gut lymphatic tissue.

Although a strong immune response is associated with an increased inflammatory profile, it could be beneficial in obesity and intestinal inflammation. For example, women are better at eliminating opportunistic and pathogenic gut bacteria that could be a byproduct of a heightened immune response.

This heightened response may be a factor that slows or protects against the development of obesity-related disorders in women. In contrast, the gut immune response in men is relatively smaller, allowing harmful microbes to enter and possibly exacerbate the development of obesity.

Final remarks

Gender differences in the pathophysiology and epidemiology of obesity place postmenopausal men and women at the highest risk of metabolic disorders. Although sex hormones/chromosomes and fat distribution serve as the basis for sexual dimorphisms, the function and composition of the gut microbiota and the gut immune system also account for these dimorphisms. More studies will be needed in the future to assess causality and identify specific imbalances in the gut microbiome that cause obesity.

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