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Longevity Briefs: Can A ‘Leaky Gut’ Make You Overweight?

Posted on 26 May 2023

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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.

Why is this research important: Not all fat tissue is bad for you. While it’s a bit of an oversimplification, fat tissue can generally be split into two types. ‘Bad’ white fat serves to store excess energy, while ‘good’ brown fat consumes energy in order to generate heat. We know that fat cells (adipocytes) can transition between brown and white in response to the environment – cold temperatures, for example, encourage fat cells to become brown. We also know that having more brown fat is associated with reduced risk of obesity and age related diseases like heart disease.

A better understanding of what affects the ‘browning’ of fat cells could be valuable for preventing and treating obesity, and could also be harnessed by people looking to lose weight. One strategy could be to target the bacteria in the gut, as the signals these microorganisms produce can enter the blood and have wide ranging consequences for the body.

What did the researchers do: In this study, researchers wanted to investigate the potential for bacteria in the gut to influence the function of fat tissue, by affecting the ability of fat cells to become brown. They collected abdominal subcutaneous fat cells (the insulating layer of fat beneath the skin) from about 150 people of various BMI classes, some of whom had undergone bariatric surgery (changes to the digestive system with the aim of promoting weight loss).

The researchers took blood samples from participants and measured the levels of endotoxin – a component of some bacteria that can sometimes leak from the gut into the blood, causing system-wide inflammation. They compared this to the expression of genes related to fat cell browning, and also studied what happened when fat cells were exposed to endotoxins outside the body.

Key takeaway(s) from this research:

  • Higher levels of endotoxin correlated with lower expression of genes related to fat cell browning
  • Exposing fat cells to endotoxin appeared to inhibit browning and increase inflammation
  • A ‘leaky gut’ could expose fat tissue to endotoxin, promoting obesity by raising inflammation and reducing brown fat formation

The researchers found that higher levels of endotoxin were associated with lower expression of browning genes, while bariatric surgery was associated with reduced endotoxin levels and improved browning gene expression relative to the untreated obese participants. 

This isn’t that surprising: there are many reasons why someone who is overweight might be more likely to have a ‘leaky gut’ and therefore more endotoxin in their blood. Poor diet and lack of exercise would be among the primary confounders, as both of these are thought to increase gut permeability. However, the researchers also found evidence that the relationship was causal. When adipocytes were exposed to endotoxins in cell culture, they expressed fewer brown fat-related genes and produced more inflammatory signals (inflammation is thought to be an important driver of weight gain). Endotoxin-treated cells also didn’t respond as well to adrenaline, the hormone that usually tells fat tissue to burn energy to produce heat.

How can you avoid a leaky gut? You should strive to follow a diet that limits processed, high-fat and high-sugar foods, and that includes sufficient amounts of fibre. Undertaking exercise and limiting your alcohol intake can be helpful. There are also some studies suggesting that probiotics can restore the integrity of the gut wall.

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    The impact of metabolic endotoxaemia on the browning process in human adipocytes

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