Story ideas from the Journal of Lipid Research

Articles published in the October 2007 issue of the Journal of Lipid Research (Vol. 48, No. 10)

ARTICLE HIGHLIGHTS

• Alternate-day fasting: How good is it for your health?

• How a statin drug reduces cholesterol and fat in blood vessels

• How nutrition affects the breakdown of fats

• Thematic Review: Intriguing structures on the surface of fat cells

Researchers report that fasting or eating half as much as usual every other day may shrink your fat cells and boost mechanisms that break down fats.

Consuming less calories and increasing physical activity is usually what people do to lose weight and stay healthy. But some people prefer to adopt a diet which consists of eating as much as they want one day while fasting the next. On each fasting day, these people consume energy-free beverages, tea, coffee, and sugar-free gum and they drink as much water as they need. Although many people claim that this diet, called alternate-day fasting (ADF), help them lose weight and improved their health, the effects on health and disease risk of ADF are not clear.

Krista Varady and colleagues studied the effects of alternate-day fasting on 24 male mice for four weeks. To assess the impact of ADF on the health of the mice, the scientists not only tested mice that followed and didn’t follow an ADF diet, but they also studied mice that followed the diet only partially: a group of mice consumed 50 percent of their regular diet every other day (ADF-50%) and another consumed 75 percent of their regular diet every other day (ADF-25%).

The scientists noticed that the mice that followed the complete ADF diet (ADF-100%) lost weight and that the fat cells of both the ADF-100% and ADF-50% groups shrunk by more than half and by 35 percent, respectively. Also, in these two groups of mice, fat under the skin – but not abdominal fat – was broken down more than in mice that did not follow the diet.

These results suggest that complete and modified ADF regimens seem to protect against obesity and type 2 diabetes but do not result in fat or weight loss. More studies will be needed to confirm whether the long-term effects of ADF regimens are beneficial for health and reduce disease risk, the scientists conclude.

Article: “Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism and plasma adiponectin levels in mice,” by Krista A. Varady, D. J. Roohk, Y. C. Loe, B. K. McEvoy-Hein, and M. K. Hellerstein

MEDIA CONTACT: Krista A. Varady, University of California, Berkeley; e-mail: kvarady@nature.berkeley.edu

Scientists have provided new details about how a drug used against heart disease helps to unclog blood vessels from an excess of cholesterol and fats. The results help explain how the drug works and may provide ways to improve similar drugs in the future.

A type of white blood cell called macrophage is responsible for the accumulation of fat in blood vessels, leading to inflammation and plaque formation on the inner linings of the vessel. Macrophages produce enzymes called lipases that have been shown to promote fat accumulation in blood vessels. Drugs called statins reduce the accumulation of fat in macrophages but their effects on lipases have not been explored yet.

John S. Hill and colleagues studied the effect of a statin drug called atorvastatin on two lipases, called lipoprotein lipase and endothelial lipase, which break down different types of fats. The researchers showed that the statin significantly reduced the levels of both lipases in macrophages and described in detail the proteins that are affected within the macrophages. These results may help to understand how other statin drugs work and could help design better drugs against heart disease in the future, the scientists conclude.

Article: “Atorvastatin Decreases Lipoprotein Lipase and Endothelial Lipase Expression in Human THP-1 Macrophages,” by Guosong Qiu and John S. Hill

MEDIA CONTACT: John S. Hill, St. Paul’s Hospital, Vancouver, Canada; e-mail: jshill@interchange.ubc.ca

Scientists have shown that when either lean or obese individuals exercise after eating a high fat meal, their fats are broken down and oxidized in skeletal muscle, making them healthier. These results show for the first time how a high fat diet and exercise stimulate the breakdown of fats and may help design ways to reduce excessive fat in the body.

Fat is broken down inside fat cells to generate energy by a process called lipolysis. The resulting fatty acids are released into the bloodstream and carried to tissues that require energy. In obese individuals, too much fat accumulates, compromising lipolysis, but the details of how this happens are not well understood. Also, obese individuals can show altered responsiveness to the stress hormones epinephrine and norepinephrine in their subcutaneous fat.

Max Lafontan and colleagues investigated how fat is broken down in both lean and obese subjects who exercised after either fasting or eating a high-fat diet. They noticed that after eating a high-fat diet, fats were broken down in both lean and obese individuals. Under fasting conditions, the breakdown of fats was more pronounced in the lean subjects, but the high fat meal enhanced lipolysis in the obese subjects.

The scientists also studied the effects of long-chain fatty acids (LCFAs) – which are found in high fat diet – on cultured fat cells. They noticed that LCFAs increase lipolysis when it is induced by epinephrine, one of the hormones known to stimulate lipolysis.

By showing for the first time how a high fat diet and LCFAs affect hormone-induced lipolysis in fat cells, this study paves the way for further research on the role of various fatty acids on the metabolism of muscle and blood vessel cells, the researchers conclude.

Article: “Acute exposure to long-chain fatty acids impairs alpha2-adrenergic receptor-mediated antilipolysis in human adipose tissue,” by Jan Polak, Cedric Moro, David Bessiere, Jindra Hejnova, Marie A. Marques, Magda Bajzova, Max Lafontan, Francois Crampes, Michel Berlan, and Vladimir Stich

MEDIA CONTACT: Max Lafontan, Institut National de la Sante et de la Recherche Medicale (French National Institute of Health and Medical Research), Toulouse, France; e-mail: Max.Lafontan@toulouse.inserm.fr

The following article is the fifth in a series of reviews on “adipocyte biology” or the biology of fat tissue. The other articles in the series will appear in future issues of the journal. All thematic review articles and can be accessed at: http://www.jlr.org/ (under “Thematic Reviews”).

The surface of fat cells contains many small pockets called caveolae (because they look like caves in an electron microscope). Although their role is not clear, Paul F. Pilch and colleagues review current knowledge about caveolae and conclude that one of their major functions is to regulate the movement and production of fats in fat cells. Caveolae may also help the hormone insulin bind to fat cells, but this is controversial.

Insulin binds to protein receptors on the surface of a fat cell, which activates proteins inside the cell that help lower the amount of sugar in the blood and store fats. Some scientists have shown that insulin receptors attach to caveolae, hinting at a possible role of caveolae in insulin function, but other scientists have disputed this finding. Also, scientists have suggested that caveolae can be absorbed inside the cell, forming spherical vesicles that may carry fats for storage in the cell.

Caveolae may also be involved in regulating the amount of fatty acids – the molecules resulting from the breakdown of fats – present in fat cells. When too many fatty acids are produced inside the cell, the caveolae act as small gates that modulate the release of excess fatty acids outside the cell. Conversely, the caveolae may also help produce fats and later store them in structures called lipid droplets, which are fat storage areas inside fat cells.

Paul F. Pilch and colleagues conclude that although previous and recent studies have revealed that caveolae play key roles in the regulation of fats, more research is needed to understand how they work as well as their molecular composition.

Article: “Cellular Spelunking: Exploring Adipocyte Caveolae,” by Paul F. Pilch, Ricardo P. Souto, Libin Liu, Mark P. Jedrychowski, Eric A. Berg, Catherine E. Costello, and Steven P. Gygi

MEDIA CONTACT: Paul F. Pilch, Boston University School of Medicine, Mass.; e-mail: ppilch@bu.edu

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society’s student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

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