Mice who received a transplant of brown fat into their abdominal cavity lost weight, improved their insulin sensitivity and metabolised glucose better says a study reported in the December issue of the Journal of Clinical Investigation available online Dec. 10. The research may offer a new treatment pathway for those suffering from diabetes and the constellation of metabolic syndromes associated with it, including polycystic ovarian syndrome.
Brown fat is not the same as white fat. In fact, it is more closely related to skeletal muscle than it is to white fat. Brown fat is thermogenic, meaning that it burns energy to create heat, whereas white fat just stores excess energy, particularly around the thighs and abdomen. Scientists have been interested in the ability of brown fat to reverse some of the metabolic changes which precede diabetes for years. In 2009, they engineered mouse and human cells to produce brown fat cells which they then transplanted into mice. Those brown fat cells then burned energy in the host mice, protecting them against obesity.
Brown fat is mostly found in newborn mammals, who are unable to shiver and animals who hibernate. It mainly occurs on the back, neck and shoulders as well as around the heart and protects the mammal from hypothermia or becoming too cold, by burning sugar and creating heat.
Brown fat is able to burn so much energy, because it has a very high number of mitochondria, little organelles within the cell which act as the powerhouses for the cell. Incidentally, this is where brown fat cells get their name from. The mitochondria contain a high proportion of iron, which makes the cell look brown. They also contain more droplets of fat than white cells, which only contain one droplet each. Brown fat has more capillaries too, as it has a higher requirement for oxygen to fuel the energy burning. White fat is associated with increased body mass, brown fat is associated with a lower body mass index (BMI).
In the current study, funded by the National Institutes of Health, a research team led by Laurie Goodyear, head of the Section on Integrative Physiology and Metabolism at the Joslin Diabetes Center in Boston and Associate Professor of Medicine at Harvard Medical School, successfully cured insulin resistance and obesity in mice who received a transplant of just 100 mg of brown fat into their abdominal cavity.
Using mice fed either a normal diet or a high-fat diet, Goodyear and colleagues demonstrated that brown fat (BAT or brown adipose tissue) transplants significantly decreased body weight and improved insulin sensitivity and glucose metabolism.
The transplanted brown fat also secreted hormones, including IL-6, which mediated metabolic effects throughout the body. This study establishes brown fat as an important regulator of metabolism and suggests that this tissue could be an important therapeutic target in the treatment of obesity-related diseases.
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By eight to twelve weeks following transplantation, the BAT-transplanted mice fed a normal diet showed improved glucose tolerance, increased insulin sensitivity, lower body weights and decreased fat mass. Three control groups, which had a WAT (white adipose tissue) transplant, a glass bead implant or surgery without transplantation, did not show any metabolic improvements.
"We were able to establish that BAT transplantation affects metabolism. This study provides further evidence that BAT is a very important metabolic organ and a potential treatment for obesity-related diseases such as diabetes, metabolic syndrome and insulin resistance"
says lead author Kristin I. Stanford, PhD, a postdoctoral fellow in the Section on Integrative Physiology and Metabolism.
The mice fed a high-fat diet also exhibited beneficial effects from BAT transplantation, including improved glucose metabolism, decreased body weight and a complete reversal of insulin resistance resulting from excess fat consumption. Previous studies of BAT transplantation in mice, which transplanted BAT in a different location and had a shorter duration, did not show beneficial effects.
The transplanted BAT affected metabolism throughout the body by increasing levels of circulating Interleukin-6 (IL-6). The researchers also found that BAT transplantation increased norepinephrine and FGF-21. IL-6 has been shown in previous studies to increase energy production and decrease body weight. When the researchers transplanted BAT from donor mice genetically engineered not to produce IL-6, the mice who received the transplants showed no metabolic improvements.
"This is the first study to demonstrate that an increase in BAT significantly increases levels of circulating IL-6. It suggests that an increase in BAT-derived IL-6 improves glucose metabolism throughout the body"
says senior author Laurie J. Goodyear, PhD, head of the Section on Integrative Physiology and Metabolism.
The researchers are following up on the study by looking into other ways BAT may have beneficial metabolic effects and further investigating the functions of IL-6 and other BAT-derived hormones, says Dr. Goodyear. Dr. Stanford is studying the relationship between BAT and type I diabetes, based on data from a collaborator that suggests that BAT may help control glucose in type I diabetes.
The researchers have demonstrated that brown adipose tissue (BAT) has beneficial effects on glucose tolerance, body weight and metabolism and the results are of considerable interest to scientists and pharmaceutical companies who are investigating ways to use brown fat as a treatment for human obesity in the future as well as diabetes and the constellation of associated syndromes including insulin resistance, polycystic ovarian syndrome and metabolic syndrome.
Brown fat is generated in humans during exposure to cold temperatures. Exercise such as swimming in unheated water, encourages the body to produce more brown fat cells.
Sources:
Kristin I. Stanford, Roeland J.W. Middelbeek, Kristy L. Townsend, Ding An, Eva B. Nygaard, Kristen M. Hitchcox, Kathleen R. Markan, Kazuhiro Nakano, Michael F. Hirshman, Yu-Hua Tseng, Laurie J. Goodyear. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. Journal of Clinical Investigation, 2012; DOI: 10.1172/JCI62308
Gesta S, Tseng YH, Kahn CR (October 2007). "Developmental origin of fat: tracking obesity to its source". Cell 131 (2): 24256.doi:10.1016/j.cell.2007.10.004. PMID 17956727.
Nedergaard J, Bengtsson T, Cannon B (August 2007)."Unexpected evidence for active brown adipose tissue in adult humans". Am. J. Physiol. Endocrinol. Metab.293 (2): E44452. doi:10.1152/ajpendo.00691.2006.PMID 17473055.
Shingo Kajimura et al. (27 August 2009). "Initiation of myoblast/brown fat switch through a PRDM16-C/EBP- transcriptional complex" (Advance Online Edition). Nature 460 (7259): 11541158.doi:10.1038/nature08262. A fat burning review can help you produce a clear summarize of what you demand to focus on to carry out your fat reduction goal if you're a beginner; or serve as a reminder for the ones who are at an intermediate or more advance phase of their weight-loss strategy. Following are seven steps that can serve as methods for your own weight loss system. The first thing that one must understand is that losing weight and losing fat is not exactly the same thing. Many weight loss programs have fooled people into thinking that it is the same, but most diets and weight loss applications only work by leading to a person's body to eliminate more muscle cells and water than actual body fat, more help please visit The Fat Loss Factor. PMC 2754867.PMID 19641492.
http://www.eurekalert.org/pub_releases/2009-07/dci-sce072709.php
http://www.joslin.org/9192.htm
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