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Title: Curcumin and piperine supplementation of obese mice under caloric restriction modulates body fat and interleukin-1beta

Author
item MIYAZAWA, TAIKI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item NAKAGAWA, KIYOTAKA - Tohoku University
item KIM, SHARON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item THOMAS, MICHAEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item PAUL, LIGI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ZINGG, JEAN-MARC - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DOLNIKOWSKI, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ROBERTS, SUSAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item KIMURA, FUMIKO - Tohoku University
item MIYAZAWA, TERUO - Tohoku University
item AZZI, ANGELO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MEYDANI, MOHSEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Nutrition and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/29/2018
Publication Date: 2/6/2018
Citation: Miyazawa, T., Nakagawa, K., Kim, S.H., Thomas, M.J., Paul, L., Zingg, J., Dolnikowski, G.G., Roberts, S.B., Kimura, F., Miyazawa, T., Azzi, A., Meydani, M. 2018. Curcumin and piperine supplementation of obese mice under caloric restriction modulates body fat and interleukin-1beta. Nutrition and Metabolism. 15:12. https://doi.org/10.1186/s12986-018-0250-6.

Interpretive Summary: Metabolic syndrome is a group of conditions that occur at the same time and increase the risk of heart disease, stroke and diabetes. These conditions include high blood pressure, high blood sugar levels, abnormal cholesterol levels and excess body fat around the waist. Developing metabolic syndrome is therefore closely associated with being overweight or obese. Reducing food intake and increasing physical activity are ways to fight metabolic syndrome. An additional approach would be to develop supplements, especially using natural substances, that enhance the metabolism of overweight persons who are going through a weight reduction program using calorie restriction. For example, curcumin, an important biological substance in the spice turmeric, appears to have anti-obesity and anti-inflammatory properties. Piperine, a biologically active substance found in black pepper, may increase the effectiveness of curcumin. Male mice were fed a high fat diet to induce obesity. One group continued on with its diet without change or supplementation. The other 4 groups underwent calorie restriction beginning at 10 percent fewer calories and later increased to 20 percent and were given different combinations of curcumin and piperine. The high fat diet mice on a 20% calorie reduction supplemented with a combination of curcumin and piperine demonstrated accelerated total body fat loss induced by the calorie restriction. In addition to this outcome, curcumin and piperine seem to be effective at suppressing inflammation induced by a high fat diet and preventing the shortening of telomeres, which cap the ends of DNA strands and are associated with cell aging. The use of natural, biologically active substances may indirectly improve the conditions that develop with metabolic syndrome by accelerating body fat loss during a weight loss regimen.

Technical Abstract: Background: Dietary bioactive compounds capable of improving metabolic profiles would be of great value, especially for overweight individuals undergoing a caloric restriction (CR) regimen. Curcumin (Cur), a possible anti-obesity compound, and piperine (Pip), a plausible enhancer of Cur's bioavailability and efficacy, may be candidate agents for controlling metabolism and health. Methods: 47 eight-week-old male C57BL/6 mice fed a HFD for 23 weeks to induce obesity. Then, mice were divided into 5 groups. Group 1 continued on HFD ad-libitum. The other four groups underwent CR (reduced 10 percent HFD intake for 23 wks, 20 percent for 30 wks) with Cur, Pip or Cur+Pip. Percent body fat, plasma inflammatory markers associated with obesity (interferon (IFN)-gamma, interleukin (IL)-10, IL-12 p70, IL-1beta, IL-6, KC/GRO and TNF-alpha), plasma Cur metabolites and liver telomere length were measured. Results: Compared to the other groups, obese mice who underwent CR and received Cur+Pip in their diet lost more fat as measured by MRI, had significantly lower IL-1beta and KC/GRO, and demonstrated a trend toward longer telomere length. Tandem mass spectrometry analysis of plasma from obese mice under CR showed no differences in Cur metabolite levels between groups supplemented with Cur alone or combined with Pip. However, plasma IL-1beta levels were inversely correlated with CurG. Conclusion: It is plausible that supplementing the high fat diet of CR mice with Cur plus Pip may reduce body fat, suppress HFD-induced inflammation and potentially prevent the shortening of telomere length. Cur and Pip have the potential to improve factors associated with metabolic syndrome.