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HomeHealth ConditionsObesityCan Inhibiting Adipose Triglycerides Fight Obesity and its Comorbidities?

Can Inhibiting Adipose Triglycerides Fight Obesity and its Comorbidities?

A new study in Nature examines the benefits of the medication Atglistatin in reducing fatty acid circulation in mice fed a high-fat diet. The results offer promise to humans in reducing obesity rates and obesity-linked diseases such as diabetes and fatty liver disease.


Obesity constitutes a growing public health problem worldwide. It occurs when there is an inequality between fat production and fat burning. When fat production exceeds fat burning, increased fatty acids are released into the body, which not only contribute to the accumulation of white adipose tissue, but also play a significant role in non-alcoholic fatty liver disease as well as insulin resistance.

Adipose triglyceride lipase (Atgl) is a primary enzyme used to intracellularly break down triacylglyserols, which are main component of body fat in both humans and mice. Past studies have shown that mice with Atgl deficiencies demonstrate enhanced glucose tolerance and insulin sensitivity, however these mice were prone to suffer from cardiac, respiratory and mitochondrial disorders.

In this recent study, Schweiger and colleagues investigate whether inhibiting Atgl using Atglistatin can counteract obesity caused by a high-fat diet, insulin resistance and liver disease in mice. The researchers studied the effects of Atglistatin on both wildtype (control) and Atgl-deficient (experimental) mice. The genotypic mice were fed a high fat diet (HFD) for 50 days and then were randomly assigned into two groups. One group continued with the HFD only, while the other received a HFD supplemented with Atglistatin over a period of 50 days. The same process was performed with the Atgl-deficient mice over a period of 40 days. The mice’s weight and food consumption were measured. Insulin and glucose testing were administered and the mice’s feces were studied to measure lipid absorption. Blood tests, tissue analysis and MRI were also performed.

The mice given Atglistatin demonstrated a 47% reduction in fatty acids compared to control mice, however, these effects in limiting lipolysis appear to be transient, lasting for approximately eight hours. Both groups that were administered Atglistatin demonstrated decreased weight gain and insulin resistance. The most notable effect of Atglistatin was a decrease in fatty liver disease. Atglistatin exerted its effects on adipose tissue and the liver and was not found to cause cardiac-related side effects in mice, even after five months of continued use.

This study offers evidence to support the remedial effects of Atglistatin on high-fat-diet influenced obesity, glucose intolerance, and fatty liver disease in mice. While Atglistatin has not been found to limit lipolysis caused by adipose triglyceride in humans, it offers the promise of future drug developments for an adipose triglyceride-inhibitor in humans, which would to not only battle obesity, but also its sister syndromes.


Written By: Allison Pitman Sevillano, MS, PT, DPT



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