Newly discovered mechanism of mitochondrial dysfunction in obesity may drive insulin resistance and type 2 diabetes (CoQ10 could help)

Medical Xpress / Harvard T.H. Chan School of Public Health / Nature ^ | May 30, 2025 | Maya Brownstein / Renata L. S. Goncalves et al

[ConservativeMind]

A newly discovered mechanism that leads to liver dysfunction may be a key factor in type 2 diabetes and other metabolic disorders in individuals with obesity, according to a new study.

The dysfunction identified—dysregulated hepatic coenzyme Q metabolism—leads to excessive reactive oxygen species (ROS) produced by mitochondria at a single specific site in an enzyme called complex I.

Mitochondria metabolize nutrients and generate the building blocks needed to maintain metabolic homeostasis. During this process, mitochondria also generate ROS—molecules that, in small, controlled amounts, are essential to support normal body functions, but that can be harmful when produced in large quantities.

Excess ROS production is a known consequence of obesity.

To advance the understanding of mitochondrial ROS (mROS) generation—and its health consequences—the researchers zeroed in on the liver, a central organ for glucose and lipid homeostasis that has never been studied in detail in terms of mROS production. The study explored all possible sources of mROS in the liver from both lean and obese mice.

It found that the obese mice's livers failed to produce proper amounts of coenzyme Q, a molecule essential to energy production. This defective coenzyme Q metabolism drives an unusual process called reverse electron transport (RET) that occurs in an enzyme called complex I, causing mitochondria to increase generation of ROS and, consequently, disrupt metabolism.

The researchers observed similar alterations in coenzyme Q metabolism when analyzing the genes and measuring coenzyme Q ratios in people with another metabolic disorder, fatty liver disease.

"We've reframed the problem from a generalized to a site-specific phenomenon, so in the future, instead of broad-spectrum antioxidants, a tailored cocktail of compounds could be developed to effectively and safely reduce mROS, either through decreasing RET, increasing coenzyme Q levels, or both to treat metabolic diseases including type 2 diabetes."

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TOPICS: Health/Medicine
KEYWORDS: liver; metabolism; mitochondria; type2diabetes

[ConservativeMind]

Coenzyme Q is the same thing as ubiquinone, CoQ10, which is available as a supplement.

Treating your metabolic disease also appears to reverse this problem.

[ConservativeMind]

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[Flaming Conservative]

So if your body does not properly metabolize CoQ10, would it do any good to supplement it?

[ConservativeMind]

This is a good insight:

It found that the obese mice’s livers failed to produce proper amounts of coenzyme Q, a molecule essential to energy production.

“We've reframed the problem from a generalized to a site-specific phenomenon, so in the future, instead of broad-spectrum antioxidants, a tailored cocktail of compounds could be developed to effectively and safely reduce mROS, either through decreasing RET, increasing coenzyme Q levels, or both to treat metabolic diseases including type 2 diabetes.”

[Rockingham]

Due to the importance to mitochondrial function, Vitamin D3 and magnesium supplementation are also in order. For the sake of better absorption, the magnesium should be as magnesium glycinate and/or magnesium L-threonate.

[SunkenCiv]

• Study shows that an anti-inflammatory diet could extend overall survival after treatment for stage III colon cancer [06/21/2025]
• Triple therapy regimen significantly improves survival in BRAF V600E-mutated metastatic colorectal cancer [06/21/2025]

[Bob434]

There are several different forms of Coq 10- and many c,aims about certain forms being more available absorption wise. I’m not sure what type is considered the best though.

[ConservativeMind]

We use Swanson ubiquinol, which is a converted form of CoQ10. It is more active and potent, so you can use less.

[Flaming Conservative]

Ah. That explains it! I’ve got some CoQ10 somewhere around here; I’ll have to dig it up.

[Chgogal]

Bookmark

[Bob434]

Thank you I will check that out. I’ve been using qunol not sure what form it is.

[Tunehead54]

For my gal - tomorrow. ;-)

[CaptainPhilFan]

Interesting. Thank you.

[AdmSmith]

Unfortunately, not a free article https://pubmed.ncbi.nlm.nih.gov/40437093/ but an earlier paper is here: “Ubiquinone deficiency drives reverse electron transport to disrupt hepatic metabolic homeostasis in obesity”

Abstract: Mitochondrial reactive oxygen species (mROS) are central to physiology. While excess mROS production has been associated with several disease states, its precise sources, regulation, and mechanism of generation in vivo remain unknown, limiting translational efforts. Here we show that in obesity, hepatic ubiquinone (Q) synthesis is impaired, which raises the QH2/Q ratio, driving excessive mROS production via reverse electron transport (RET) from site IQ in complex I. Using multiple complementary genetic and pharmacological models in vivo we demonstrated that RET is critical for metabolic health. In patients with steatosis, the hepatic Q biosynthetic program is also suppressed, and the QH2/Q ratio positively correlates with disease severity. Our data identify a highly selective mechanism for pathological mROS production in obesity, which can be targeted to protect metabolic homeostasis.

https://www.biorxiv.org/content/10.1101/2023.02.21.528863v1.full.pdf

[sauropod]

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