Sex steroids, insulin and fat metabolism: implications for healthy aging

As part of the ISGE symposium on Day 3, we heard from Tommaso Simoncini on the implication of sex steroids, insulin and fat metabolism on healthy ageing.

One of the most prominent changes during menopause is fat gain and change in a women’s body shape. At the moment we struggle to have a good understanding of the reason for this change. Unlike other menopausal transitions, hormonal interventions currently available are not targeting this issue. These changes are serious as they are not just an aesthetic alteration but can have a negative impact on overall health. The Interheart study and recent data from the WHI, show it’s the site of fat that’s the biggest cause for concern as an increase in abdominal fat is linked to increased CVD risk.

Research into this area over the last few years has shown that fat accumulation is different in each person.  In fact unlike many people expect it’s not just the obese that are at risk there are lean people who carry multiple cardiometablic risk factors, typically referred to as metabolically obese, normal weight (MONW), they are often characterised by; excess visceral adipose tissue and extopic fat deposition, adipose tissue inflammation, altered inflammatory and adipokine profiles, reduced skeletal muscle mass and low cardiorespiratory fitness.

Data from the WHI observation study showed women can be separated into four sections; metabolically benign normal weight, at risk normal weight, metabolically benign overweight and at risk overweight. These four categories scored very differently showing links between phenotypes, metabolic type and insulin resistance. Looking at women who have features of metabolic syndrome, showed they had higher markers such as IL-6. The very skinny or the very obese are more at risk than those who are or moderately obese.

But is this related to menopause or aging?

During menopausal transition women have a reduction of vaspin and visfatin which result in less insulin sensitivity and more adipsin resulting in more insulin secretion. The SWAN study showed that across the menopausal transition women don’t increase body weight or percentage body fat, however their fat distribution changes. Vaspin was found to be an important characteristic; women who don’t suffer from metabolic syndrome have a reduced amount of vaspin circulating. Healthy women lose concentration of vaspin during menopausal transition but those that aren't a healthy weight don’t. More research into this relationship is required.  

Obesity happens due to change in energy balance, as people don’t have the ability to burn energy compared to what they intake. To avoid diabetes, the fat storage must expand which is a scavenger to worse metabolic conditions, this can be done by expanding fat or increasing insulin secretion by the pancreas. The increase in visceral fat during menopause therefore may be a protective factor.

Testing is now taking place to look at the effect of estrogen, testosterone, and progesterone on SGBS cells, to look the role of sex hormones with insulin signalling in fat cells. Data has demonstrated an increased amount of lipid droplets in cells with addition of estrogen, testosterone, progesterone, so we know sex steroids alter the ability of differentiation of adipocytes and may have a part to play.

Healthy ageing is impacted by genes, hormones, diet, habits, physical activity, social activity and mental activity, so whilst we continue to look at if hormones can help with healthy ageing, lifestyle changes must be made.