Skeletal Muscle Development Responds To Nutrient Availability

[Guest guest]

Skeletal Muscle Development Responds To Nutrient Availability

http://www.medicalnewstoday.com/articles/107183.php

A new study finds that restricted nutrient availability prevents

muscle stem cells from growing into mature muscle cells. The

research, published by Cell Press in the May issue of the journal

Developmental Cell, provides exciting new information about how

developing muscle cells sense and respond to nutrient levels. The

study adds a new twist to ongoing research into the effects of

caloric restriction on physiology and aging and may lead to new

therapeutic avenues for muscle wasting.

Although it is certainly rational to expect that access to nutrients,

such as the simple sugar glucose, has a profound impact on the

development of human cells, the cellular strategies for responding to

fluctuations in nutrient availability are not well understood. Drs.

Vittorio Sartorelli and Marcella Fulco from the National Institutes

of Health investigated how the availability of glucose affects the

ability of muscle stem cells, called myoblasts, to develop

(or " differentiate " ) into mature skeletal muscle fibers.

The researchers found that glucose restriction (GR) impaired

differentiation of skeletal myoblasts and activated AMP-activated

protein kinase (AMPK). These results define a pathway in which

activation of AMPK in response to low glucose levels stimulates

expression of the NAD+ biosynthetic enzyme Nampt. NAD+ is a known

cofactor of SIRT1, which plays an important role in numerous

physiological processes, including differentiation of skeletal muscle

cells, and has been implicated in regulation of lifespan and aging.

Importantly, inhibition of AMPK, Nampt or SIRT1 resulted in skeletal

muscle cells that were oblivious to a nutrient poor environment and

were able to differentiate under conditions that otherwise would not

be suitable.

These results demonstrate that a defined pathway actively controls

muscle differentiation in response to low nutrients. " We speculate

that, functioning as a cellular checkpoint, the AMPK-Nampt-SIRT1

pathway may be activated by reduced nutrient availability to prevent

cells from undertaking energy demanding processes - such as cell

differentiation - during calorie-unfavorable conditions. On the other

hand, once nutrients become available, the pathway is inactivated to

allow resumption of physiological development, " offers Dr.

Sartorelli.

The study has important implications that extend beyond muscle

development. This mechanism also operates in adult tissues and thus

would be part of the response to a dietary regimen that restricts

caloric intake. Further, the researchers found that glucose

restriction or treatment of skeletal muscle cells with metformin, a

drug used to treat type II diabetes, had similar outcomes and

resulted in the activation of SIRT1. " It is therefore possible that

the well-known benefits that diabetics derive from lowering the

calorie intake in their diet may be attributable to activation of the

AMPK-Nampt-SIRT1 axis " comments Dr. Sartorelli. It is also attractive

to speculate that AMPK and SIRT1 may prove to be rational targets for

counteracting the devastating effects of muscle wasting.