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Longevity

Longevity Briefs: Why Exactly Is Visceral Fat Bad – And A Potential Dietary Solution

Posted on 15 October 2024

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

When it comes to ageing (and health in general) not all fat tissue is equal. White fat tissue – especially visceral fat (abdominal fat that surrounds important organs) – is associated with increased risk of diabetes and other age-related disease. But why exactly is visceral fat bad? We know that visceral fat accumulates during ageing and that visceral fat cells become senescent – that’s when cells permanently stop dividing. Senescent cells are thought to play an important role in ageing through multiple mechanisms, including promoting inflammation in surrounding tissue. However, we don’t know exactly why visceral fat cells seem prone to senescence. 

In this study, researchers focus on chemicals called lipid enals. These are a class of compounds that are created when the lipids in cell membranes are oxidised. Enals accumulate at high levels in visceral fat during ageing and can easily pass through cell membranes to damage proteins and DNA, which might be an important cause of senescence in this tissue.

The discovery:

By experimenting with human lung cells and mouse stem cells, researchers showed that common enals were quick to trigger senescence, at least in cell culture. The main mechanisms for this seemed to be damage to DNA, which activated genes and signalling pathways to trigger senescence, as well as damage to proteins within the mitochondria. This results in inefficient production of the ‘cellular fuel’ ATP and increased production of harmful byproducts, which together may contribute to ageing.

The researchers then tried treating mice that had been fed a high-fat diet with L-carnosine in their drinking water. L-carnosine is a peptide produced by the liver and found mainly in muscle and brain tissue. It can bind to enals to prevent them from reacting with anything else. Researchers found that mice treated in this way had fewer markers of senescence and improved blood sugar control compared to untreated mice, but mice fed a normal diet (rather than the high fat diet) were still much better off in both regards.

Changes in blood glucose over time (minutes) as a percentage of fasting blood glucose in mice after receiving a glucose-rich meal. Mice were fed a high fat high sucrose diet (HFHS) as well as carnosine (yellow), HFHS without carnosine (red) or a control diet with no added carnosine (blue).
Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells

The implications:

This research sheds some light on how exactly visceral fat is promoting senescence and accelerating the development of age-related disease. In doing so, it also hints that dietary strategies could mitigate some of the effects of visceral fat. The healthiest dietary sources of L-carnosine are poultry and fish. Plants like asparagus, green peas and white mushrooms are good sources of beta-alanine and histidine, the two amino acids that make up L-carnosine, and so can support its synthesis despite not containing L-carnosine itself.

However, it’s clearly far more beneficial to avoid accumulating visceral fat in the first place. We also have to keep in mind that the mouse experiments in this study were small, and used an inbred strain of mice that develop a lot of health problems that normal mice don’t, so they’re not great models for human health. On the other hand, there is already some human evidence that L-carnosine supplementation may be beneficial in humans with diabetes mellitus while also potentially delaying sarcopenia and cognitive decline.


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    References

    Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells https://doi.org/10.1111/acel.14367

    Carnosine and Beta-Alanine Supplementation in Human Medicine: Narrative Review and Critical Assessment https://doi.org/10.3390/nu15071770

    Title image by Siora Photography, Upslash

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