OMNI investigates the causes of obesity and its complications, as well as the molecular, cellular and physiological regulation of energy balance and metabolic function.

The Obesity, Metabolism and Nutrition Institute (OMNI) at Massachusetts General Hospital conducts clinical trials, genetic studies, and basic and mechanistic research on obesity and its related disorders.

OMNI uses a variety of research techniques to develop a better understanding of obesity and its causes. This includes enrolling patients in clinical trials to test the efficacy of treatments, studying the human genome to unlock the genetic underpinnings of obesity and using lab models to gain a better understanding of the effectiveness of obesity treatments so we can better predict outcomes for patients.

Clinical Trials Provide Access to Innovative Therapies

The clinical research studies conducted at OMNI focus on the underlying physiological mechanisms that promote obesity and related comorbidities. Such mechanistic studies may help to identify types of obesity based on differing biological bases. A thorough understanding of the many different types of obesity will help physicians make treatment decisions in the future.

OMNI's clinical trials also provide an opportunity to assess new and innovative ways to treat obesity and give patients access to potentially valuable treatments while being safely monitored and evaluated.

Several trials are currently in progress. They include studies to:

  • Assess the efficacy of a novel device for the treatment of obesity and type 2 diabetes
  • Develop a less invasive test for the progression of nonalcoholic fatty liver disease
  • Assess the effect of weight loss after bariatric surgery on brain natriuretic peptide hormone and cardiovascular disease
  • Determine the effect of fecal microbial transfers on weight loss in patients with obesity
  • Assess the use of pharmacological treatments for obesity, including specific sequences and algorithms for their use, novel combinations of medications, medications paired with lifestyle therapies and medications with or after bariatric surgery

Additional trials of pharmacological, nutritional, behavioral and surgical interventions are in the planning stages.

Investigating the Genetics of Obesity

In addition to developing new therapeutic approaches to treat obesity, OMNI also conducts research to identify the genetics that cause obesity. OMNI recently completed a genome-wide association study (GWAS) of 1,000 Mass General patients with severe obesity who have undergone bariatric surgery.

The study was conducted to assess the contribution of genetics to obesity and its related disorders. These studies have confirmed some of the previously known genes related to obesity, lipid disorder and diabetes. In addition, these studies demonstrated a strong genetic contribution to weight loss outcome after gastric bypass and identified a genetic change present in some individuals that is associated with the amount of weight loss.

Ongoing studies of genetic contributors to metabolic disease are aimed at identifying additional predictors of disease course and therapeutic outcome for obesity, diabetes, fatty liver disease and other metabolic disorders.

To complement these studies, OMNI has recently begun to examine whether patterns of gene expression could be used to determine the results of different treatments.  For these studies, gene expression patterns in tissues from patients who have exhibited profound weight loss from Roux en-Y gastric bypass (RYGB) have been compared with gene expression patterns in tissues from patients who have experienced only modest weight loss from RYGB.

By assessing genetic and clinical information from these patients, OMNI hopes to identify factors that predict successful weight loss following bariatric surgery. This information may someday help physicians target specific therapies to the patients who will most benefit from them.

Mechanistic Studies Investigate the Biology of Obesity

Understanding the biology of obesity and related diseases can help identify ways to improve treatment results. Through laboratory research, various gastrointestinal weight loss procedures are studied, including RYGB, duodenojejunal bypass, adjustable gastric banding (AGB), sleeve gastrectomy, ileal interposition and endoluminal duodenal sleeve implantation, as well as numerous variations and modifications of these procedures.

Through these studies, we have demonstrated that:

  • RYGB, AGB, sleeve gastrectomy, endoluminal duodenal sleeve and duodenojejunal bypass induce substantial weight loss (generally 10-20% of initial body weight) in animals with diet-induced and genetic obesity
  • These procedures induce weight loss by different mechanisms
  • These procedures have variable effects on insulin signaling and diabetes
  • Gastric procedures primarily affect food intake and body weight
  • Intestinal procedures have a lesser effect on food intake, but a greater effect on glucose homeostasis
  • Gastric bypass substantially affects energy expenditure
  • Intact hormone signaling between the gut and central nervous system (CNS) is required for changes in food intake but not changes in energy expenditure after RYGB
  • RYGB blocks responsiveness to the food environment in animals that would be otherwise be susceptible to diet-induced obesity
  • The composition of the gastrointestinal microbiota population is altered by RYGB
  • The effect of microbiota on weight and adiposity can be transferred from host to recipient

Current studies include:

  • Determining the molecular and cellular mechanisms by which bariatric surgery affects metabolic physiology
  • Deciphering the mechanism by which microbiota alter metabolism
  • Determining other changes in gastrointestinal physiology, communication between the gut and CNS, and behaviors that contribute to weight loss after RYGB
  • Assessing the relative contributions of different components of gastric bypass and other gastrointestinal procedures on weight loss and other metabolic functions
  • Determining other metabolic effects of RYGB, including the effects on insulin secretion, fat metabolism, micronutrient absorption and calcium/bone metabolism