A pot belly and a metabolism gone haywire in middle age? Here’s why your waistline is growing

Only a few manage to avoid it. We’re talking about the waistline expanding as the years go by. Once you’ve passed the ‘forties’ mark, the risk of developing a paunch gradually increases, even if your overall weight doesn’t necessarily go up. The problem is that this redistribution of fat tissue, which causes the waistline to widen gradually, leading to an ‘apple-shaped’ figure, is not exactly harmless from a metabolic point of view. The increase in intra-abdominal fat, in fact, slows down the metabolism, leads to the production of substances that certainly do not promote wellbeing, and promotes inflammation. The result is that, ultimately, the risk of developing diabetes increases, as do the risks of suffering a heart attack or stroke and other chronic conditions affecting the kidneys and liver. But how does this sort of ‘toll’ that the body pays as it ages come about? Research published in *Science* (lead authors Guan Wang, of City of Hope, and Gaoyan Li, of the University of California, Los Angeles – UCLA) offers a possible biological explanation that could account for the changes in fat distribution. The process is apparently ‘driven’ by a type of adult stem cell that emerges as the ageing process progresses and which promotes the production of fat cells.

The research, carried out in collaboration with experts from the Arthur Riggs Diabetes & Metabolism Research Institute at City of Hope and the University of California, Los Angeles, has identified a new type of stem cell that appears during ageing and which may contribute to the production of new fat cells. Starting with an analysis of ‘white’ adipose tissue – the type that is metabolically most harmful to health and which, in a sense, acts as a ‘storehouse’ for accumulating abdominal fat – the experts sought to look beyond cellular hypertrophy – that is, the increase in the volume of adipocytes typical of advancing age. Instead, their research began by examining the increase in the number of abdominal adipocytes – a factor potentially involved in the development of a growing waistline – and thus the mechanisms leading to the emergence of new fat cells. In this regard, to determine whether and how the numerical growth of fat cells might influence the development of a ‘belly’, the scientists focused their attention on adipocyte progenitor cells (APCs), stem cells found in adipose tissue which, as precursors, can mature into mature adipocytes.

The research involved transplanting APCs taken from young and older animals into a group of young mice. It was at this stage that it became apparent that the APCs from the older animals gave rise to a large number of adipocytes. Conversely, when APCs from young animals were transplanted into older mice, the growth of adipocytes was limited. This is the first evidence of the ability of older APCs to produce large quantities of fat, regardless of the animal receiving them. But that is not all. Analysis using single-cell RNA sequencing – designed to assess gene activity in individual cells – revealed that APCs are relatively inactive in young mice, whilst in middle-aged animals their activity increases exponentially, stimulating the production of a vast number of fat cells. “Whilst the growth capacity of most adult stem cells declines with age, the opposite is true for APCs: ageing unlocks these cells’ ability to develop and proliferate,” commented one of the study’s authors, Adolfo Garcia-Ocana , in a press release from City of Hope . “This is the first evidence that our waistlines expand with age due to the high production of new fat cells by APCs.”

To complete the picture, the researchers also observed that the effects of senescence go beyond the activation of APCs. In middle-aged animals, these cells have in fact transformed into age-specific differentiated preadipocytes (CP-A). These cells emerged specifically during ageing and have proven particularly effective at producing new fat cells. Their emergence may help explain why older mice accumulate more fat as they age. Not only that: the researchers have also identified specific biological signals that drive the growth of these cells in older animals. In short: as another author of the study, Qiong (Annabel) Wang, the study found that “ageing triggers the emergence of a new type of adult stem cell and increases the body’s massive production of new fat cells, particularly in the abdominal region”. As if that were not enough, the researchers identified cells that closely resembled the newly discovered CP-A cells, and found that these were present in greater numbers in the tissues of middle-aged individuals.

This finding paves the way for possible future treatments to control and prevent excessive abdominal fat. “Understanding the role of CP-A cells in metabolic disorders and how these cells emerge during ageing could lead to new medical solutions to reduce abdominal fat and improve health and longevity,” concludes Wang. “It has long been known that adipose tissue contains stem cells: in this case, we are talking about a time-dependent change in the stem cells within this tissue,” comments Annamaria Colao, Vice-President of the Higher Health Council. At present, it seems crucial to focus solely on visceral fat, and future experiments will help us in this regard. But we must not forget that, according to a very important study published some time ago in the New England Journal of Medicine, being slightly overweight is beneficial for longevity after the age of 65: life expectancy is in fact lower among both obese and underweight individuals. In short: whilst it is true that, over time, a ‘right’ amount of fat may have a protective effect, if this mechanism were to be triggered too early – with the negative effects of visceral fat – it would become important to control it.”