A new UCI-led study finds that your genetic gender determines the way your muscles “talk” to other tissues in your body

Newswise – Irvine, CA – May 31, 2022 A new study at the University of California, led by Irvine, has identified sex-specific circuits of muscle signals to other tissues and that the effects of organs and processes on muscles differ markedly between males and females. This new discovery provides insight into how muscles work, such as exercise, promote healthy longevity, metabolism, and improve cognition.

The study is entitledBiological sex and sex hormones dominate the genetic variation of putative myokinetic signalingPosted in eLifeis the first to evaluate how genetic architecture affects muscle signaling to other tissues, highlighting that sex and estrogen are critical determinants of these processes.

“Muscle is essential for maintaining a metabolic state, and disruption of muscle function is a hallmark of diseases such as obesity, type 2 diabetes and cardiovascular disease,” said the study’s senior author. Marcus M. Selden, Ph.D.assistant professor of biochemistry at the University of California College of Medicine.

Muscles secrete proteins called myokines, which play roles in a variety of processes by interacting with other tissues. Essentially, myokines allow skeletal muscle to communicate with organs such as the kidneys, liver, or brain, which is necessary for the body to maintain its metabolic homeostasis. Some of the processes performed on myokines include inflammation, cancer, changes induced by exercise, and even cognition. Despite the clear relevance of myokines to many physiological consequences, the way in which these proteins are regulated and their effects is not well understood.

In this study, the research team conducted a survey of genetic associations focused on myokinetic gene regulation, muscle cell formation, cross-tissue signaling, and genetic-sex interactions in humans. While the expression levels of the majority of myokins and cell lineages within skeletal muscle showed few relative differences between males and females, nearly all important cross-tissue enrichments function in a sex-specific or hormone-dependent manner; In particular, with estradiol. These sex- and hormone-specific effects were consistent across the main metabolic tissues: liver, pancreas, hypothalamus, intestine, heart, visceral and subcutaneous adipose tissue. This study highlighted some examples such that the muscular signals of the pancreas are greater in females, compared to males where the liver is predominant.

“We already know that skeletal muscle plays an essential role in coordinating physiological homeostasis. In this study, we sought to understand how muscle interacts with metabolic tissues and to illustrate the importance of considering the effects of genetic sex and sex hormones when studying metabolism,” Selden said.

Going forward, the research team plans to create cell-based systems to evaluate some of the new hormones revealed as part of this study and investigate why their signaling differs between the sexes.

This work was supported by the National Institutes of Health.

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