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Excess dietary carbohydrate affects mitochondrial integrity as observed in brown adipose tissue

Waldhart AN, Muhire B, Johnson B, Pettinga D, Madaj ZB, Wolfrum E, Dykstra H, Wegert V, Pospisilik JA, Han X, Wu N. (2021) Cell Rep  36(5) 109488. doi: 10.1016/j.celrep.2021.109488. 

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Abstract:

Hyperglycemia affects over 400 million individuals worldwide. The detrimental health effects are well studied at the tissue level, but the in vivo effects at the organelle level are poorly understood.

To establish such an in vivo model, we used mice lacking TXNIP, a negative regulator of glucose uptake.

Examining mitochondrial function in brown adipose tissue, we find that TXNIP KO mice have a lower content of polyunsaturated fatty acids (PUFAs) in their membrane lipids, which affects mitochondrial integrity and electron transport chain efficiency and ultimately results in lower mitochondrial heat output.

This phenotype can be rescued by a ketogenic diet, confirming the usefulness of this model and highlighting one facet of early cellular damage caused by excess glucose influx.

Keywords: BAT; PUFA; TXNIP; cold stress; glucose; ketogenic diet; lipid; mitochondria.

FAB RESEARCH COMMENT:

These findings add to the existing evidence that diets high in sugar and/or refined carbohydrates (which convert rapidly to glucose) can impair energy metabolism.

They also identify a new mechanism by which this happens - namely, by altering the fatty acid composition of mitochondrial membranes.

A low-carb and high-fat (ketogenic) diet reversed the energy production problems in the animals studied here.   Importantly, however, these mice were specially selected for difficulties in regulating glucose uptake (in order to study this in depth).

Results from animal studies can never be taken as generalising automatically to humans - but they can allow investigation of basic shared mechanisms that cannot be studied directly in humans.

As the researchers highlighted, these results help to explain the well-known links between high-sugar diets and many different metabolic diseases, and may also point the way towards new and better management approaches.


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