Unlocking mitochondria’s role in fat metabolism could pave the way for new metabolic disease therapies, study reveals

22 Dec 2023 --- Fat is a diet component essential to the supply of vital building blocks and aiding vitamin absorption, yet its excessive consumption can lead to metabolic diseases. New research offers insights into how the roles of mitochondria — organelles acting as powerhouses of the cell — in fat transportation in the body and in ensuring balanced lipid homeostasis could provide new solutions to these health concerns.

“This discovery marks a significant leap forward in understanding the crucial role of mitochondria in dietary lipid transport and metabolism,” says Dr. Chrysanthi Moschandrea, a postdoctoral researcher at the University of Cologne Graduate School on Aging (CECAD), Germany, and the lead author of the study.

A key finding of the study is that when the mitochondria do not function as they should, enterocytes — the intestinal lining cells — show impaired packaging and transport of lipids in the form of chylomicrons. These are ultra-low-density lipoproteins responsible for transporting dietary lipids from the intestines elsewhere in the body, making them essential to the absorption of nutrients. 

“These findings provide new perspectives for the better understanding of the gastrointestinal symptoms in patients suffering from mitochondrial disease and may also lead to new therapeutic approaches,” adds CECAD collaborator Professor Aleksandra Trifunovic.

This disturbed functioning of the mitochondria in the intestines led to the abnormal accumulation of dietary fat.Mitochondrial function 
The study published in the journal Nature discusses how mitochondrial dysfunction, specifically the deficiency of the DARS2 gene — crucial in the production of mitochondria — leads to impaired chylomicron production and transport of dietary lipids to peripheral organs. 

Mice with a DARS2 deficiency experienced a disruption of regular mitochondria functioning in their intestines. Their enterocytes contained large fat droplets, affecting the mice’s growth. According to the researchers, this fat build-up hinders fat delivery to peripheral organs. 

More specifically, the study’s findings suggest that mitochondrial dysfunction impedes the transport of chylomicrons within cells through the endoplasmic reticulum — a cell’s transportation system — to the Golgi — a cell organelle that plays a role in processing and packaging proteins and lipid molecules. This dysfunctioning results in lipid storage in large droplets within the cell. 

At the same time, feeding mice a fat-free diet alleviated this fat build-up, which indicates the symptom originates from digested fat. 

Dietary fats 
A study published earlier this year similarly highlighted the dangers of high-fat diets, finding that while such diets can lead to short-term weight management improvement by leading to a decrease in calorie consumption, they can also result in long-term weight gain as they tend to increase appetite after a longer period.

Mice consuming a high-fat diet were also observed to be suffering from inflammation, which could affect appetite by inducing detrimental effects on the brain, resulting in the larger size of the region of the brain responsible for controlling appetite. 

Meanwhile, a recent study on muscle endurance among the elderly has revealed that proper mitochondrial function is also essential to the performance of muscle cells.

Research also indicates that a healthy and balanced gut microbiome is important to the maintenance of healthy mitochondrial function. 

By Milana Nikolova