A novel pathway to combat obesity through browning of bone marrow adipose tissue

Prof. Rivka Dresner-Pollak, M.D., Dept. of Endocrinology & Metabolism

The prevalence of obesity continues to increase throughout the world resulting in impaired health (type 2 diabetes, cancer, high blood pressure, cardiovascular disease, stroke, kidney disease, asthma, osteoarthritis, dementia, etc.). In fact, obesity is the fifth leading factor for global deaths. Adipose tissue or body fat consists of three main fat depots: visceral, subcutaneous and marrow. Visceral fat (white) located inside the abdominal cavity is much more plentiful than brown fat and is the predominant form of fat in the body, originating from connective tissue. Visceral fat is the more dangerous fat since an excess of white fat inside the belly is associated with an increased risk for heart disease, diabetes, and cancer. On the other hand, brown fat, originally thought to be present in neonates only, has beneficial metabolic effects and stimulating its generation is a much desired goal in combating obesity. New research shows that when people overeat, they not only increase their total amount of white fat, but the overconsumption results in their brown fat becoming dysfunctional and thus unable to burn calories. Subcutaneous fat (also white) is more desirable physiologically, however it is unsightly and is of concern to people who are worried about their appearance. Everyone has subcutaneous fat, but some people have more than others, probably determined by genetics.

There are treatments that are targeted to combat obesity such as 1) bariatric surgery which is an invasive procedure that reduces the size of the stomach and has to be done by a highly experienced surgeon. Bariatric surgery in older patients has also been a topic of debate, centered on concerns for safety in this population; the relative benefits and risks in this population is not known. And of course, 2) a healthy non-fat diet and regular exercise which have been proven that the majority of people do not adhere to.

Recent data has indicated that marrow adipose tissue (MAT), a heterogeneous fat depot which has emerged as a fat depot with a key role in whole body fat and energy metabolism. MAT content has been poorly examined in obesity. Like all other endocrine organs, MAT participates in body fat metabolism and can undergo pathologic changes, thus it can play an important role in combating obesity. Using knockout mice, i.e., mice in which a target gene is inactivated, Prof. Dresner-Pollak and her research team have recently discovered that Sirtuin1, a protein which plays a role in aging and metabolism, regulates the bone marrow adipocytes and induces a brown-adipocyte like program in MAT via a novel mechanism.

Scientists have found that lean people tend to have more brown fat than obese people and that when it is stimulated, it can burn white fat. Thus, Prof. Dresner-Pollak’s research is of the utmost importance since she is undertaking a promising anti-obesity treatment investigation which would set the stage for the design of novel bone marrow-based therapies to combat obesity and metabolic diseases. This discovery could lead to new methods for weight loss since brown fat takes calories from excessive accumulation of white fat and burns it. As this field is highly competitive, Prof. Dresner-Pollak is looking for financial support to move this research forward quickly and obtain DEXA, a bone density measurement machine which can also be equipped with a software that will measure regional fat mass (marrow, visceral and subcutaneous) and body composition. This equipment is important to analyze MAT development in metabolic diseases.