Main Submission Volume 3/Issue 1/2012 HealtH S cience i nquiry Volume 3 / Issue 1 / 2012 70 Molecular, Genetic and Clinical Research in Obesity and Diabetes Bomhof (UCalgary) Marc R. Bomhof University of Calgary Obesity and associated chronic disease has seen a dramatc rise in the past 30 years. 1 Although the etology of obesity is multfaceted and extremely complex, obesity can be distlled down to positve energy balance. When energy absorbed by the body exceeds energy expended, weight gain is achieved. As the global trend in obesity persists, it is clear that restoring the energy homeostasis equaton back to equilibrium remains somewhat of an elusive task. Recently, gut bacteria, or gut microbiota, and the associated short chain faty acids (SCFA) that they produce have emerged as new players in energy balance and may yield the ability to restore equilibrium. The precise role these bacteria are playing, however, remains somewhat of a mystery. There are approximately ten tmes more bacteria cells in the colon than cells in the human body. Comprised of nearly 2000 species and containing around 100 trillion cells, the gut microbiota weighs approximately 1kg and yields a genome size 100 tmes greater than the human genome. 2 Given the vast ‘microbiome’ lying in close proximity to the lining of the intestnes, microbiota are thought to functon as a ‘metabolic organ’ within the host, providing metabolic and endocrine functon, immune system development, and protecton against pathogens. Through the process of fermentaton, bacteria are able to harness energy from the otherwise indigestble foods entering the colon, producing a range of metabolic by-products such as vitamins, SCFAs (butyrate, propionate, acetate), amino acids, and other odoriferous volatle organic compounds. From a metabolic health and energy balance perspectve, these metabolites (in partcular SCFA) seem to have a lot of infuence. Research over the past several years has demonstrated the ability of gut microbiota to promote positve energy balance. In studies conducted by Gordon and colleagues, germ free (bacteria free) mice were found to have 40% less total body fat than mice with a ‘normal’ gut microbiota. When the germ free mice were re-inoculated with gut bacteria, total body fat increased by 60%. 3 Additonal studies have found that germ free mice resist weight gain associated with a western diet. 4 According to the authors, these fndings can be atributed to a reducton in SCFA producton in the gut and benefcial changes in host gene- expression that limit depositon of fat in adipocytes. Notng that the gut microbiota of lean versus obese individuals are dominated by diferent bacterial phyla groups, research by Turnbaugh and colleagues established that an obesity- associated gut microbiota was more efcient at extractng energy (SCFA) from feces. 5 Confrming these fndings, a recent human study found that bacterial groups commonly found in obesity are associated with increased energy extracton from stool. 6 Despite gut microbiota and SCFA being charged with promotng positve energy balance, there is a wealth of evidence that highlights the ability of SCFA-producing bacteria to improve metabolism in favour of a lean phenotype. Supplementaton with prebiotc fber, a non- digestble food ingredient that is highly fermented in the cecael-colon by Bifdobacterium spp., consistently reduces body weight, adipose tssue mass, and consumpton of calories. SCFAs, produced from the fermentaton of prebiotc fber, are believed to mediate these efects. Peptde YY, an anorectc hormone that is increased with prebiotc fber, is reputed to be released from intestnal L-cells afer actvaton of a G protein-coupled receptor by SCFA. 7,8 Interestngly, the same G protein-coupled receptors that are found on intestnal L-cells are also found in adipose tssue. SCFA binding to these receptors has been shown to suppress the release of free faty acids into the blood stream, which can limit the uptake of fat and development of insulin resistance in non-adipose tssues. 8 Additonally, research by Cani and colleagues has established that bifdogenic prebiotcs increase the producton of glucagon- Gut bugs, energy balance, and obesity