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Bone Marrow Fat Tissue Secretes Hormone
That Helps Body Stay Healthy

Bone marrow has been known for its flavorful addition to soups and as a delicacy for dogs but its fat also may have untapped health benefits, new research finds.

A University of Michigan-led study shows that the fat tissue in bone marrow is a significant source of the hormone adiponectin, which helps maintain insulin sensitivity, break down fat, and has been linked to decreased risk of cardiovascular disease, diabetes, and obesity-associated cancers. The findings appear online, ahead of print in Cell Metabolism.

Bone marrow adipose tissue primarily has been associated with negative health effects, most notably because of a documented relationship to reduced bone mass and increased risks of fractures and osteoporosis. However, the new study—which included people with anorexia, patients undergoing chemotherapy, rabbits, and mice—suggests that this type of fat also may have benefits.

“These findings are significant because we’ve found that bone marrow adipose tissue may have positive, protective roles, and influence adaptive functions outside of the bone tissue, at least during calorie restriction,” says senior author Ormond MacDougald, PhD, the John A. Faulkner Collegiate Professor of Molecular & Integrative Physiology, a professor of internal medicine, a member of University of Michigan’s Brehm Center for Diabetes Research, and a Fulbright Scholar at the University of Cambridge in the United Kingdom.

“We know that low adiponectin has been correlated with multiple health problems and our findings suggest that an important source of this protein, and potentially others that we haven’t identified yet, is the fat tissue inside bone marrow,” says colead author Erica Scheller, DDS, PhD, a University of Michigan postdoctoral fellow in the MacDougald lab.

Researchers have long studied the function of fat, or adipose tissue, in hopes of better understanding the link between obesity and ill health. One possible link is adiponectin, a hormone produced by adipose tissue that helps preserve insulin action. High levels of adiponectin are linked to decreased risk of diabetes and cardiovascular disease. People with obesity have the lowest levels of adiponectin, potentially increasing their risk of developing such diseases, while the leaner someone gets, the more adiponectin they have.

An outstanding question in the field has been why adiponectin increases as people lose body fat. A limitation in understanding this paradox is that previous research has focused on peripheral white adipose tissue, which has been believed to be the sole source of adiponectin.

The new study finds that bone marrow fat tissue, which increases as body weight falls, is a previously unrecognized source of adiponectin during calorie restriction.

The study found that both marrow adipose tissue and adiponectin increased in humans with anorexia and in patients undergoing chemotherapy or radiation treatment for ovarian or endometrial cancer. Researchers next used mice to study what happens when marrow fat formation is blocked and found a relationship between bone marrow adipose tissue and adiponectin, indicating that fat tissue in marrow can have effects beyond the bone.

“Bone marrow adipose tissue has traditionally had a bad reputation because of its relationship to decreased bone mass but we now know that adipose tissue within marrow goes beyond the bone and also serves as an endocrine organ that can influence metabolism,” says colead author William Cawthorn, PhD, a University of Michigan postdoctoral fellow in the MacDougald lab. “These findings really underscore how little we know about marrow adipose tissue and also the mechanisms affecting circulating adiponectin levels. This is really just the beginning of much further research to better understand these relationships and their implications.”

— Source: University of Michigan Health System

 

Drug Shows Promise for Effectively Treating Metabolic Syndrome

University of Utah researchers have discovered that an enzyme involved in intracellular signaling plays a crucial role in developing metabolic syndrome, a finding that has a University of Utah spinoff company developing a drug to potentially treat the condition.

The researchers, led by Jared Rutter, PhD, a professor of biochemistry, hope to begin human clinical trials of the drug in the next couple of years.

“The approved drug therapies do not treat or prevent this condition in most people,” says Rutter, senior author of a study describing the research published in Cell Reports. “But given the results of our research with mouse and rat models, we are hopeful that metabolic syndrome can be effectively treated with drug therapy someday soon.”

Metabolic syndrome, a group of conditions that increases the risk of developing heart disease, diabetes, and stroke, is estimated to affect up to 25% of adults. Public health officials believe metabolic syndrome has reached epidemic proportions in the United States and elsewhere.

Metabolic syndrome includes disorders such as high blood pressure, high blood sugar levels, abnormal cholesterol readings, and obesity. One of the prominent features of the syndrome is the excessive production and storage of fatty acids and triglycerides.

In research with rodents, Rutter, Xiaoying Wu, and Allen Nickols of BioEnergenix, a University of Utah spinoff company that Rutter cofounded in 2009, discovered that an enzyme known as PASK stimulates the overproduction of fatty acids and triglycerides. PASK works by chemically modifying other proteins in order to alter their specific functions. One of the proteins it modifies is SREBP-1c, which functions as the master regulator of all of the enzymes that make fat.

Using a drug candidate being developed by BioEnergenix, the researchers prevented PASK from modifying SREBP-1c. This, in turn, prevented SREBP-1c from increasing the production of enzymes that make fat, resulting in a drop in the levels of fatty acids and triglycerides in mouse and rat livers. Insulin resistance and diabetes also were partially reversed in diabetes-prone animals.

“We hope that this is an example where science leads us not only to a better understanding of how the body works, but also to the discovery of approaches that we can use to treat human disease,” Rutter says.

Researchers don’t know what causes fatty acids and triglycerides to be overproduced, and that will be a focus of Rutter’s ongoing research as well as trying to understand how PASK activates SREBP-1c.

— Source: University of Utah Health Sciences