NGFN-PLUS

Weight cycling does not affect longevity in two different mouse strains

Coordinator:    Prof. Dr. Matthias Blüher
Institution: Universität Leipzig
Homepage: www.atherobesity.de
The majority of obese patients can not maintain hypocaloric diets over a longer period of time. As a consequence weight cycling is a frequent phenomenon in longterm treatment of obesity. Long-term studies on weight cycling and intentional weight loss suggest that non-pharmacological and non-surgical treatment of obesity might entail elevated mortality rates. Therefore, we tested the hypothesis that weight cycling reduces life span in comparison to both permanent hypercaloric and normal nutrition in two different mouse strains.
The research goals of this project were:

1)    identify genes/ genetic regions and molecular mechanisms, which protect C57Bl6 mice in contrast to 129S6/Sv mice against the adverse effects of weight cycling on life-span (using 129S6/Sv X C57Bl6 intercross F2 mice)

2)    define the effects of chronic subclinical environmental lipophilic toxin exposure (benzpyrene, food contaminants: Di-(2-ethylhexyl-phthalate (DEHP), Bisphenol A (BPA) tributyltin, (TBT)) on longevity on models of weight cycling compared to normal diet, continuous high fat diet and life long caloric restriction.

3)    to functionally characterize and validate novel obesity genes identified in WB1 and to study the expression of these candidate genes as a molecular basis for new treatment strategies in human cross-sectional (fat depot specific expression) and interventional (diet, exercise, bariatric surgery) cohorts and animal models of obesity.

In 129S6/SvEvTac (N=100) and C57BL/6NTac (N=100) the effects of a continuously caloric restriction, a life-long high fat diet (Sniff, E15772-34) and  weight cycling, which was realized with a 4 week period change between both extremes of diet, on longevity have been determined. Body weight was recorded weekly. Intraperitoneal insulin tolerance (ITT) test was performed at the age of 24 and 51 weeks and the HbA1c was analyzed at the age of one year. Basal metabolic rate was measured with metabolic chambers (TSE, Bad Homburg, Germany). The average life expectancy for weight cycling animals (129S6/SvEvTac average age at death: 21.5±5 month and C57BL/6NTac 21.5±3.5 month) was comparable with the controls under chow diet (129S6/SvEvTac average age at death: 23.5±5 month and C57BL/6NTac 21.1±4 month). The permanent high caloric diet group had a 3.5 month shorter life span than the two other groups (129S6/SvEvTac average age at death: 20.5±5 month and C57BL/6NTac 17.1±4.8 month). 129S6/SvEvTac mice lived 1.5 months longer than C57BL/6NTac mice. In addition, significant differences between the dietary regimens were found for measures of insulin sensitivity (ITT), glucose metabolism (HbA1c) and energy expenditure. In conclusion, frequent weight cycling significantly improved longevity compared to a lifelong high fat diet. There was no difference in the life span of mice undergoing weight cycling and permanent chow diet.


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