Obesity fragments Mitochondria to become dysfunctional due to one gene

Good news! Perhaps a breakthrough and opportunity for new treatment!

"... In their new study, an international team of researchers found that when they fed mice a high-fat diet, mitochondria within the mice's fat cells broke apart into smaller mitochondria, which had a reduced capacity for burning fat.

They also discovered this process is governed by just one gene. When they deleted that gene from their test subjects, the mice avoided excess weight gain – even when fed the same high-fat diet that wreaked havoc in other mice. ..."

From the abstract:

"Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction."

Obesity Disrupts Mitochondria, And We May Have Figured Out How : ScienceAlert

How Obesity Dismantles Our Mitochondria UC San Diego study reveals key mechanism behind obesity-related metabolic dysfunction

Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation (open access)

These colored streaks are mitochondrial networks within fat cells. Researchers from UC San Diego discovered that a high-fat diet dismantles mitochondria, resulting in weight gain.

Fig. 4: Rala knockout in white adipocytes increases mitochondrial activity and fatty acid oxidation via preventing obesity-induced mitochondrial fission in iWAT.