About 59 million American adults are classified as obese, with a body mass index (BMI) greater than 30 kg/m2. Serious cardiometabolic health threats linked to obesity (e.g. diabetes, heart disease, stroke) threaten about 30% of the American population. The aging population may be at particular risk, as over 50% of middle aged adults are expected to gain excess weight. Interestingly, excess weight gain and an increased risk for metabolic disorders is also observed in the circadian desynchronized population (e.g. night shift workers and otherwise healthy, non-breakfast eaters). Investigating the interaction between circadian rhythms, aging and body weight is a new avenue for exploration. Broadly, this proposal studies the environmental and genetic interactions which lead to weight gain in the aging and circadian desynchronized population and possible therapeutic interventions for its prevention. Specifically, this proposal utilizes an innovative, environmental protocol (i.e. desynchronized feeding, DF) which causes a misalignment between the circadian light cycle and metabolic expression. This environmental intervention is then applied to genetic models (i.e. C57BL/6J and Clock mutant mice) of varying ages to determine the gene-environment interactions leading to weight gain associated with age and DF. Using this approach, this proposal investigates three specific hypotheses: 1) that age and DF additively affect energy expenditure, 2) that age can exaggerate metabolic impairments during DF, and 3) that DF alters circadian clock and metabolic gene expression in brain and peripheral tissues. The goals of this proposal can be achieved through a rigorous research training plan which focuses on integrating molecular techniques, genetics, and physiological measurements of body weight and metabolism. This proposal aims to uncover new mechanisms leading to weight gain and is expected to lead to new insights and therapeutic approaches designed for the treatment and prevention of obesity, diabetes and other cardiometabolic disorders all age groups as well as in the circadian desynchronized population.
This proposal is expected to lead to new insights and therapeutic approaches designed for the treatment and prevention of obesity, diabetes and other cardiometabolic disorders in which the aged and circadian desynchronized population are particularly vulnerable.
| Arble, Deanna Marie; Vitaterna, Martha Hotz; Turek, Fred W (2011) Rhythmic leptin is required for weight gain from circadian desynchronized feeding in the mouse. PLoS One 6:e25079 |
