America's Healthier Coffee: Metabolism

Friday, January 4, 2013

Brown Adipose Tissue Beneficial For Metabolism And Glucose Tolerance

Main Category: Diabetes
Also Included In: Obesity / Weight Loss / Fitness
Article Date: 12 Dec 2012 - 1:00 PST Current ratings for:
Brown Adipose Tissue Beneficial For Metabolism And Glucose Tolerance
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Joslin Diabetes Center scientists have demonstrated that brown adipose tissue (BAT) has beneficial effects on glucose tolerance, body weight and metabolism. The findings, which may lead to new treatments for diabetes, appear in the upcoming issue of the Journal of Clinical Investigation.

Unlike the more prevalent white adipose tissue (WAT or white fat) which stores fat, BAT (or brown fat) burns fat to produce heat. Studies in mice and humans have suggested that BAT also plays a role in regulating body weight and metabolism. This has made BAT the focus of considerable interest among scientists and pharmaceutical companies who are investigating ways to use BAT as a treatment for obesity.

The Joslin researchers were interested in learning whether BAT is involved in glucose metabolism and uncovering the mechanisms underlying BAT's effects on metabolism and body weight. The study involved the transplantation of BAT from male donor mice into the visceral cavities of mice which were fed a standard or high-fat diet.

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 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 1 diabetes (T1D), based on data from a collaborator that suggests that BAT may help control glucose in T1D.

Dr. Goodyear and the research team are very interested in using their findings to develop new therapies for diabetes. "We hope that manipulating BAT will help people with type 1 and type 2 diabetes," says Dr. Goodyear.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our diabetes section for the latest news on this subject.
Study co-authors include: 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, all of Joslin Diabetes Center.

The study was funded by the National Institutes of Health.

Joslin Diabetes Center

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Monday, July 9, 2012

Watching Lipid Metabolism In Live Zebrafish To Learn About Fat

Main Category: Cholesterol
Also Included In: Diabetes; Obesity / Weight Loss / Fitness; Heart Disease
Article Date: 30 Jun 2012 - 0:00 PDT Current ratings for:
Watching Lipid Metabolism In Live Zebrafish To Learn About Fat
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In mammals, most lipids (such as fatty acids and cholesterol) are absorbed into the body via the small intestine. The complexity of the cells and fluids that inhabit this organ make it very difficult to study in a laboratory setting. New research from Carnegie's Steven Farber, James Walters and Jennifer Anderson reveals a technique that allows scientists to watch lipid metabolism in live zebrafish. This method enabled them to describe new aspects of lipid absorption that could have broad applications for human health. Their work is published in Chemistry & Biology.

The small intestine is composed of multiple cell types. It is also the site of microorganisms, bile and mucus that help digest and absorb food. In this environment, dietary lipids are digested by enzymes and bile so that the body, via the absorptive cells of the intestine called enterocytes, can take in critical nutrients.

One type of lipid, cholesterol, is known to impact a number of highly prevalent human diseases and is absorbed by enterocytes. In zebrafish and humans, newly absorbed cholesterol combines with proteins to form lipoproteins, vehicles destined for the lymphatic system for subsequent distribution throughout the body. In humans, a protein called NPC1L1 (short for Niemann-Pick disease, type C1, gene-like 1) plays an important role in absorption by the enterocytes, but how this protein facilitates cholesterol's journey through the cell is poorly understood.

Another lipid metabolic product, called fatty acids, are absorbed by these same cells. Despite years of study, the physiological process by which proteins mediate the initial steps of fatty acid uptake is unclear. Once absorbed, the fatty acids are converted to triacyglycerides (fat) and either prepared to be transported out of the cell or transformed into droplets of stored fat. How these fat droplets form inside intestinal cells is not well understood.

These processes involving fatty acids, triacyglycerides and cholesterol influence each other in poorly understood ways. For example, it has long been known that the presence of dietary fat increases dietary cholesterol absorption, but the mechanism by which this occurs has not been determined.

Enter Farber and his team's new research tool.

They developed a method for using fluorescently glowing forms of lipids to observe fat and cholesterol absorption in the small intestines of live zebrafish. Using this tool, they were able to demonstrate the following: The physiological processes regulating fatty acid absorption and cholesterol absorption are linked, as was first suggested by studies involving rats in the 1960s. A fatty acid called oleic acid can greatly increase the uptake of dietary cholesterol. The subcellular location of the human protein NPC1L1, suspected to regulate cholesterol absorption, is modulated by the presence of oleic acid. (Farber's team inserted the human NPC1L1 protein, fused to a red fluorescent protein, into the zebrafish.) In the presence of an abundance of dietary triacyglycerides, absorbed fatty acids were rapidly stored as lipid droplets. In contrast, cholesterol was stored in special structures, called endosomes,which are distinct from lipid droplets in zebrafish intestines. "Historically, the zebrafish has been used in the field of embryology and development and we felt that it had been underutilized for studies of whole-animal physiology," Farber said. "Using the zebrafish in this novel way allowed us to be the first to observe cholesterol absorption in a living vertebrate system."

Zebrafish studies may enable a better understanding of human fat and cholesterol metabolism and contribute to ongoing efforts to reduce the impact of diseases associated with altered lipid metabolism, such as diabetes, obesity, and cardiovascular disease.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cholesterol section for the latest news on this subject. This research was funded by NIH, the American Heart Association, the G. Harold and Leila Y. Mathers Charitable Foundation, and the Carnegie Institution for Science endowment.
Carnegie Institution Please use one of the following formats to cite this article in your essay, paper or report: