Hormones, Weight Regain, Inflammation, and Grapes

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Hormones, Weight Regain, Inflammation, and Grapes

With or without the 5 pound microbial mass residing in our inner-tube of life, the gut and its related incretin hormones comprise a powerful metabolic organ. The May 2012 issue of Diabetologia discuss the progress that has occurred in the field of incretin hormones-intestinal derived metabolic and appetite sensing hormones. In 1986 Nauck and colleagues were the first to report that individuals with type-2 diabetes had reduced levels of the gut-derived hormones GLP-1 and CCK. Fast forward 26 years later and we now have an expanded understanding about how to optimize these gut-derived metabolic hormones through surgical intervention, pharmaceuticals and most importantly, through the use of a nutritional means such as probiotics, prebiotics and pea-protein, among others


As rates of obesity exceed 35% of the U.S. adults, should we pay more attention to the optimization of gut-derived appetite regulatory hormones? How much impact do these incretin hormones have on the high rate of weight regain associated with dieting and weight loss? 

According to the May 2012 edition of Nature Medicine, as caloric intake begins to feel the immediate response of the body is to increase the production of ghrelin and decrease PYY, CCK and GLP-1. UK based Rachel Larder of the Metabolic Research Laboratory in Cambridge, discusses some important human studies confirming this barrier to long term success with diet-induced weight loss. Of particular importance are the findings of a 10-week, low-calorie-diet weight loss study in which appetite regulatory hormones were measured in 36 obese individuals at three different time intervals throughout the course of study (Sumithran 2011). Larder et al report, “….circulating mediators of appetite regulation never returned to pre-intervention levels…” and stayed depressed for more than 12 months after the study (See Figure below). Larder believes this is why more than 30% of the initial weight lost was actually regained during year-one after the low-calorie diet .


Optimizing metabolic control and improving body composition are not only important for looking good on the beach this Summer, but maybe particularly protective in the context of inflammation and cancer prevention. The May 2012 edition of Current Diabetes Reports featured a review article highlighting that the increased incidence of cancer mortality in Chinese type 2 diabetes now exceeds that of cardiovascular disease, 24.5% VS 23.5% respectively. 

Why you might ask? Well the hyperglycemichyperinsulinemic, acidic and inflammatory environment characteristic of metabolic dysfunction and diabetes favors cancer cell growth.

What about diet and exercise? Research from Seattle’s Fred Hutchinson Cancer Research Center reported data from a 1-year diet and exercise intervention trial involving 439 overweight and obese, postmenopausal women. The outcome: significant reductions inflammatory biomarkers related to inflammation (hs-CRP, IL-6 and neutrophil levels).

A study in the Journal of Nutritional Biochemistry highlights a new mechanism by which Resveratrol (the agent found largely in red wine and grapes) offsets high-fat diet induced insulin resistance. Preliminary research suggests that Resveratrol- a phytoestrogen– may work it’s metabolic magic through tickling of Estrogen Receptor alpha (ERα), indirectly enhancing the expression and translocation of the GLUT4 receptor in skeletal muscle; culminating in improved insulin sensitivity and greater metabolic flexibility.


References

Mudaliar, S., & Henry, R. R. (2012). The incretin hormones: from scientific discovery to practical therapeutics. Diabetologia. doi:10.1007/s00125-012-2561-x

Larder, R., & O’Rahilly, S. (2012). Guts over glory—why diets fail. Nature Medicine, 18(5), 666–667. doi:10.1038/nm.2747

Kong, A. P. S., & Chan, J. C. N. (2012). Cancer Risk in Type 2 Diabetes. Current Diabetes Reports. doi:10.1007/s11892-012-0277-4

Imayama, I., Ulrich, C. M., Alfano, C. M., Wang, C., Xiao, L., Wener, M. H., Campbell, K. L., et al. (2012). Effects of a Caloric Restriction Weight Loss Diet and Exercise on Inflammatory Biomarkers in Overweight/Obese Postmenopausal Women: A Randomized Controlled Trial. Cancer Research, 72(9), 2314–2326. doi:10.1158/0008-5472.CAN-11-3092

Sumithran, P. (2011). Long-Term Persistence of Hormonal Adaptations to Weight Loss. NEJM, 365(17), 1597–1604. 

Tan, Z. (n.d.). Caveolin-3 is involved in the protection of resveratrol against high-fat-diet-induced insulin resistance by promoting GLUT4 translocation to the plasma membrane in skeletal muscle of ovariectomized rats. The Journal of Nutritional Biochemistry. 2012 Advanced Online Press

Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice. Molecular and Cellular Endocrinology, 358(1), 127–134.

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