Changes in genetic expression during weight loss and weight maintenance

by Amanda Jensen* 

Losing weight is an ambition with no end. To get fit, live longer, reduce injury, look better, feel better and sleep better will pave the road toward your skinny. Yes, losing weight is known to help the heart and boost insulin sensitivity, but the question still asked is: how?

There are differences between losing weight and keeping it off. From the Department of Clinical Sciences Malmo in Sweden, researchers found seven key genes expressed in adipose tissue (fat tissue) that change with weight loss and weight maintenance—a finding that brings science one step closer to understanding how the body responds to and regulates fat loss.

This randomized controlled trial shows that the genes expressed by adipose tissue change when an obese person trims down, and stays down. "For most people," the authors report, "maintaining a reduced weight is a difficult but important task to fully obtain the beneficial effects of weight loss."
Researchers placed 12 obese adults on a low-calorie diet for three months. After subjects lost 10 percent of their body weight, they embarked on a weight-maintenance program for an additional six months. The researchers took biopsies of adipose and blood samples at baseline, immediately following weight loss, and after the period of weight maintenance.

The participants had an average reduction of almost 19 percent of body weight, the researchers report. If trimming down wasn’t news enough, immediately following the weight-loss phase, insulin sensitivity and blood triglycerides improved. Improvements to HDL (the "good" cholesterol) were realized after weight loss had been sustained.

Gene Interactions

In total, the researchers reported 2,163 genes were affected during weight loss and 1,877 different genes were modified during weight maintenance. Two genes that were among the most strongly expressed, CETP and ABCG1, are likely responsible for the improvements to HDL observed after sustained weight loss. A high HDL gives the body has a greater capacity to clear cholesterol from the tissues and send it back to the liver to be recycled or excreted. Both genes code for enzymes that promote cholesterol transfer to HDL—lowering cholesterol is a way that weight loss may be effective for bolstering heart health.

Most dieters have found that the body really resists weight change. Researchers found that expression of the weight-guarding gene CIDEA was higher when the subjects were working to maintain their weight loss. In mice, blocking expression of CIDEA prevents weight gain during over-feeding. The increased expression of CIDEA in individuals trying to maintain weight loss supports the notion that the body defies shedding pounds by dropping metabolic rate.

A person carrying too much weight is also carrying too much stress for their body. Many of the problems linked with obesity occurs because the body to trying to cope. The researchers focused on two genes; MMP9 and TNMD, which were down-regulated as a result of weight loss and weight maintenance. MMP9 and TNMD are genes that may be responsible for adaptations in conditions like obesity and metabolic syndrome.

MMP9 codes for a matrix metallopeptidase. The structure of a cell is often referred to as a matrix, think of the scaffolding in building that can be moved, modified, or degraded. These metallopeptidases are the contractors for cells. Fewer MMPs means that fewer cells are broken down and fewer are built up. The result is perhaps more, but smaller fat cells.

TNMD codes for a protein tenomodulin: the contractor (or modulator) of the blood vessels. TNMD is higher in obese individuals and has been linked to fat mass as well as poor blood sugar control. The authors write that "taken together, low amounts of tenomodulin and matrix metallopeptidase 9 or related proteins may be important for the beneficial effects of weight loss."

Keeping the Weight Off

Adipose tissue, once thought to be a dormant receptacle of energy stores and an extra layer of insulation, is a metabolically active organ. Yes, fat cells do function and perform work. According to these researchers, they contain genes that affect immune response, hormonal balance, and even metabolism—all involved in creating a "set point" for weight.

Weight loss is no easy feat, especially when the body finds security in fat. Losing weight can feel like an uphill battle, the yo-yo dieting, and perpetual cycles of weight loss and weight gain do not do anyone any favors. With weight loss the body begins to fight for its fat stores; hormones change, satiety is impaired, and metabolic rate shifts. This resilience, according to researchers, is largely a product of the genes being expressed.

"Future research on the beneficial effect of weight loss should focus on long-term effects assessed after a period of weight stability" recommend the researchers. These results provide exciting insights into the physiology of fat and its genetic adaptations. Anyone can lose weight but, according to the authors, sustaining it is the true battle with true benefit.

Reference

Johansson, L., Danielsson, A., Parikh, H., Klintenberg, M., Norstrom, F., Groop, L., & Ridderstrale, M. (2012). Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance American Journal of Clinical Nutrition DOI: 10.3945/ajcn.111.020578

*Introducing the wicked-smart Amanda Jensen, in her first guest appearance on the Evolving Health blog. She enjoys science, writing, Indian food, traveling to all sorts of places, and playing tennis. She's also a good friend to have in case you're ever in need of in-depth conversation about lipid metabolism. She's also a recent graduate of Arizona State University's nutrition program. Congrats!