Shihuan KuangShihuan Kuang's research into the inner workings of fat and muscle could yield new treatments for obesity and Type 2 diabetes, as well as higher-quality meat products. (Photo by Tom Campbell)

Muscular Mysteries

Insights Into Muscle Science Improve Human Health and the Meat We Eat

By Natalie van Hoose - Published December 10, 2014

Muscles set us in motion. Our every movement—the swing of a tennis serve, a sneeze, the blink of an eye—is powered by muscles, triggered into action by signals cabled down from the neurons in our brain. The human body houses more than 650 muscles, comprising about 40 percent of the body's total mass and driving motor function and athletic performance.

But muscles are more than just the jocks of the body. They are as crucial to our health—and as vulnerable to disease—as other tissues, such as the brain and heart. Together, muscles also form the largest regulatory organ of the endocrine system and metabolism, roles that are still not thoroughly understood.

One of the researchers advancing our knowledge of muscle biology is Purdue animal scientist Shihuan Kuang. His work focuses on how muscles develop and regenerate as well as the functions they play in communication—how they respond to neurons and how they transmit messages via hormones to other tissues and organs, such as fat and the liver. His research in muscle science has important implications for two areas that may not seem to share much in common: the meat production industry and human health.

Yet the underlying science between these fields is "remarkably similar," Kuang says. "The goals of meat production are to increase muscle mass and quality. And in the human arena, there are diseases that waste muscle, which we're working to stop or prevent. The basic science behind both of these areas involves the development of muscle and how stem cells function in muscle repair."

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From Neon Neurons to Satellite Cells

illustration of the leg muscles of a bicyclist while pedaling 

Kuang's interest in muscles was sparked by his training at Washington University in St. Louis with Joshua Sanes, the biologist who developed the famous "Brainbow" mouse. Neurons in the brain of the Brainbow mouse were individually tagged with a spectrum of fluorescent colors, allowing researchers to track their connections to specific muscles. As Kuang followed the neon paths down to twitching muscles, he became intrigued by motor control.

He honed in on satellite cells, stem cells in the periphery of muscle tissue that contribute to muscle growth and repair. The unspecified nature of satellite cells allows them to become other cell types during development or after an injury to the muscle, repairing wear and tear.

"If you sprain your ankle or run too fast, satellite cells are activated from their dormant state," Kuang says. "They divide, and a portion of these cells becomes specified and fuses with the muscle to fix the injury."

Researchers had previously assumed that all stem cells were identical, but Kuang discovered that satellite cells are organized into a hierarchy with a few more "primitive" cells giving rise to the rest. These primitive cells offer significant benefits to medicine because they are the progenitors of all other muscle cells. The finding opened up new avenues for therapies to treat severe muscle injuries and neuromuscular diseases.

Kuang also found that stem cell transplantation, a widely used treatment for muscle-wasting diseases, is far more effective if the stem cells are raised in an oxygen-poor environment similar to that found in human muscle tissue.

Before Kuang's discovery, stem cells were typically cultured in open-air conditions. Healthy stem cells were then transferred to the weak or wasting muscles to replace damaged cells and restore the strength of the tissue. But the survival rate of these stem cells was staggeringly low—only about 1 in 100 cells lived after transplantation.

"That was an indication to me that there was something in their environment they weren't happy with," he says.

Kuang deduced that a petri dish exposes stem cells to far higher levels of oxygen than they would encounter in the body: Oxygen levels in muscle tissue can fluctuate wildly, particularly when the tissue is damaged or regenerating. Growing stem cells in surroundings that mimicked these less stable oxygen levels boosted their post-transplantation survival rate sixfold, a "huge improvement," he says.

What Muscle and Fat Talk About

Meat production also depends on stem cells to mediate muscle growth. Satellite cells can be stimulated to improve the growth efficiency of animals, and adipose stem cells give rise to fat, which contributes to marbling—the interweaving of muscle and fat tissue, an important quality trait of meat products. Kuang's research team has mapped the origin of fat cells in the muscle with the goal of improving marbling in meat. The team also studies the ways in which muscle and fat regulate one another.

"Interestingly, fat and muscle stem cells frequently ‘talk' to each other," he says. "Muscle cells can send messages that cause fat to shrink or expand, while fat stem cells are required for the regeneration of injured muscles."

Understanding the "crosstalk" between fat and muscle could lead to ways of stimulating the formation of fat in animal muscle tissue in order to improve meat quality.

"A good steak has tiny pieces of fat dispersed evenly throughout the muscle," Kuang says. "That's what makes it tender and juicy. Identifying the factors that muscles use to control fat could help us manipulate that marbling process."

Kuang's work has also yielded new insights into brown fat, the heat-producing material that keeps human infants and hibernating animals warm. He collaborated with scientists at Harvard to show that brown fat shares a common ancestor with muscle tissue—not white fat, the main culprit in weight gain. Brown fat can break down the lipids stored in white fat, converting them to heat. Kuang found that a key cell-signaling pathway contributes to the development of white fat and suppresses the formation of brown fat in the human body. Together, these findings offer promising new targets for treating obesity and Type 2 diabetes.

"We now have a whole new means of understanding how fat is controlled at the molecular level," he says. "We're continuing to investigate how we can make more brown fat and how we can turn muscle or white fat into brown fat. This is potentially a powerful anti-obesity tool."

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Cell signaling pathway linked to obesity, Type 2 diabetes

Building Better Beef

Brad Kim
Brad Kim advises consumers to buy meat based on how long it has been aged and to look for brands that guarantee flavor. Color is not a reliable indicator of quality, he says. (Photo by Tom Campbell)

Animal scientist Brad Kim is taking a fresh approach to aging meat. A renowned expert in meat color, Kim explores how the aging process can enhance beef's palatability while providing benefits to human health.

He is in search of the perfect parameters for dry aging meat, a process that boosts tenderness and flavor. Dry aging involves placing unpackaged meat in a designated cooler for a period of 14 days to several weeks, causing the meat's surface to dehydrate and condense. As the meat ages, naturally occurring enzymes break down the muscle structure, and proteins in the muscle tissue are degraded, releasing amino acids and peptides. When the meat is ready for retail, the surface is cut away, revealing a deep cherry-red interior that yields unique, nutty flavors once cooked.

The process is expensive and requires strict hygienic conditions: Processors must tightly control temperature, humidity and airflow.

"Dry aging meat is really an art," Kim says. "There's no one proven way of dry aging, although it's been practiced for a long time. I am trying to identify the dry-aging conditions that will yield the best meat quality."

Kim is also parsing out the fatty acids and amino acids generated by dry-aged meat in an attempt to pinpoint the source of its distinct flavors. He has found that dry aging liberates a higher number of essential amino acids than wet aging, the standard processing method in which meat is packaged and kept in a cooler for a shorter time. Some of the amino acids and peptides produced by the dry-aging process could be beneficial to human health, he says, "an intriguing outcome."

Kim is investigating ways of naturally bolstering the number of these amino acids—which include disease-preventing compounds, antioxidants and antimicrobial agents—in meat. He also hopes to develop new food ingredients derived from meat compounds, which could be added in powder form to other food products such as energy bars, cereal and desserts to boost their nutritional properties.

"Many proteins in meat are understudied and underutilized," Kim says. "There is strong potential to use these proteins as a novel source of food ingredients to improve human health."