Research Highlight

Taking out the NASH

Newsweek has called NASH “the 21st century’s looming public health threat.” Mirroring the obesity epidemic, nonalcoholic steatohepatitis — also known as nonalcoholic fatty liver disease — affects up to 25 million adults in the United States, and many will learn of the danger only when liver failure is imminent.

Jiandie Lin, Ph.D., a faculty member at the University of Michigan Life Sciences Institute, explains how he and his lab have been investigating the molecular mechanisms underlying the development and progression of NASH, and opportunities they have uncovered for potential new treatments.

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The rising obesity epidemic has brought with it an army of maladies. One, in particular, is threatening to outpace many of the disorders that accompany obesity, in terms of occurrence and severity: nonalcoholic fatty liver disease. 

“I think in the coming decades, it’s going to be a bigger problem than even diabetes,” says University of Michigan cell biologist Jiandie Lin, Ph.D., senior author of a new study that identified a key driver of the progression to the most harmful form of the disease: nonalcoholic steatohepatitis, or NASH.

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Your Muscles Can 'Taste' Sugar

It's obvious that the taste buds on the tongue can detect sugar. And after a meal, beta cells in the pancreas sense rising blood glucose and release the hormone insulin—which facilitates the sugar entering cells where it can be used by the body for energy.

Now researchers at the University of Michigan Life Sciences Institute have uncovered an unexpected mechanism of glucose sensing in skeletal muscles that contributes to the body’s overall regulation of blood sugar levels.

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Liver Pathway Linked to Negative Impacts of High- fat, High-cholesterol Diet

It's no secret that a high-fat, high-cholesterol "junk food" diet has been linked to major health problems, including high blood cholesterol and the buildup of plaques in the arteries, known as atherosclerosis.

Research led by the University of Michigan Life Sciences Institute has identified a pathway in the liver, controlled by a protein known as BAF60a, that contributes to these negative effects by stimulating the production of bile—which helps the body to absorb more cholesterol and other fats from the foods we eat.

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Newly Discovered Hormone Points to Potential Treatment for Obesity, Type-2 Diabetes, Fatty Liver Disease

Researchers at the University of Michigan have discovered how a previously unknown hormone serves as a messenger from fat cells to the liver and are investigating the potential of developing a new treatment for metabolic disorders.

Jiandie Lin of the Life Sciences Institute described how in mice the hormone, NRG4, is secreted by so-called brown fat cells and communicates with the liver to regulate the conversion of sugar into fat. Mice without NRG4 became obese and developed hallmarks of type 2 diabetes and fatty liver disease. When scientists genetically elevated NRG4 levels in these mice, however, the animals were protected from these metabolic disorders when fed a high-calorie, high-fat diet. The research was published today in Nature Medicine.

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Lin Lab Gets to The Heart of How Niacin Works and Points to A New Pathway

High blood lipids are a leading risk factor for developing heart disease, which is the leading cause of death in the United States. Approximately one of every six adult Americans has high blood cholesterol and every 25 seconds, an American will have a heart attack, and nearly one every minute will die from it.

Blood lipids are made up of cholesterol and triglycerides that circulate in the body as lipoproteins. Statins are most commonly prescribed to treat patients with high cholesterol and fibrates and niacin are used to reduce blood triglyceride levels.

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Most life on earth, whether simple or complex, flows with the universal hum of circadian rhythms. Our sleeping, eating, and the way we burn energy are all governed by the ticking of our body clocks in relation to light and dark cycles.

Besides making us feel alternatively tired or wakeful, this 24-hour rhythm pulses with biochemical reactions throughout the body, turning on and off genes that instruct the liver to pump glucose, synthesize cholesterol, or burn fat. However, the means by which these processes are coordinated has been a mystery, until now.

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Jiandie Lin is featured twice in this month's issue of Nature for his discoveries related to the PGC-1α protein and its impact on circadian rhythms.

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