Energetic Capacity Of Skeletal Muscle: The Role of Fat-generated Hormone Adipone

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The Fat-generated Hormone Adiponectin Plays An Important Role In The

Energetic Capacity Of Skeletal Muscle

http://www.medicalnewstoday.com/medicalnews.php?newsid=46653

This is according to a new study in the July, 2006, Cell Metabolism,

published by Cell Press. Adiponectin is unusual among fat hormones in

that its levels generally decline in those who are obese.

The researchers report evidence in people and mice, linking low

adiponectin levels to insulin resistance and reductions in the number

of " cellular power plants " called mitochondria in skeletal muscle.

The findings suggest that therapies designed to boost the adiponectin

signal might prove beneficial for the treatment of insulin resistance

and diabetes, they said.

" We have discovered a skeletal muscle pathway by which adiponectin

increases mitochondrial number and function and exerts antidiabetic

effects, " said lead author Civitarese from Pennington

Biomedical Research Center in Baton Rouge, Louisiana.

Mitochondria utilize nutrient components, including fats and

carbohydrates, to generate usable energy. The number of mitochondria

therefore influences the way that muscles function. For example,

people who exercise regularly have more mitochondria in their muscles

than do those who are sedentary.

Earlier studies found that obese individuals and those with type 2

diabetes have reduced adiponectin concentrations, the researchers

said. The new study examined the effects of that reduced adiponectin

on skeletal muscle.

The researchers first examined children whose parents had type 2

diabetes and those with no family history of the disease. Muscle

taken from individuals prone to diabetes was insulin resistant and

had lower than normal concentrations of mitochondrial enzymes,

suggesting some dysfunction, they found. The level of adiponectin

also correlated with the estimated number of mitochondria in the

muscle samples.

Further study of adiponectin-deficient mice similarly found that the

animals were resistant to insulin and exhibited deficits in

mitochondria in their skeletal muscles.

Finally, the researchers showed that adiponectin treatment of human

muscle tissue in culture sparked the production of mitochondria. The

treatment also limited the production of harmful free radicals, or

reactive oxygen species, a sign that the mitochondria were operating

more efficiently.

The current findings, together with earlier studies that showed that

adiponectin increases glucose uptake from the blood stream, suggest

that the hormone might have therapeutic potential for those with

insulin resistance or type 2 diabetes, Civitarese said.

However, adiponectin itself is difficult to produce in the quantities

that would be required for a drug, he added.

" It may be that a mimetic drug that acts like adiponectin might prove

beneficial, " he said.

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The researchers include E. Civitarese, Barbara Ukropcova,

Carling, Hulver, Ravussin, and Steve R. of

the Pennington Biomedical Research Center in Baton Rouge, LA; Ralph

A. DeFronzo of the University of Texas Health Science Center in San

, TX; Lawrence Mandarino of the University of Texas Health

Science Center in San , TX and Arizona State University in

Tempe, AZ.

This study was supported partly by RO1 AG20478 (ER); DK04796 (LJM);

DK066483 (LJM); M01RR001346 (LJM), DK24092 (RAD) and

USDA20033432314010 (SRS).

Civitarese et al.: " Role of adiponectin in human skeletal muscle

bioenergetics. " Publishing in Cell Metabolism 4, 75-87, JULY 2006 DOI

10.1016/j.cmet.2006.05.002 http://www.cellmetabolism.org/