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POTENTIAL ROLE OF MELANOCORTIN 4 RECEPTOR IN PHYSICAL ACTIVITY ENERGY EXPENDITURE IN RATS: EFFECT OF CALORIE RESTRICTION

Almundarij, Tariq

Abstract Details

2015, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Tariq, Almundarij, PhD, December 2015 Physiology POTENTIAL ROLE OF MELANOCORTIN 4 RECEPTOR IN PHYSICAL ACTIVITY ENERGY EXPENDITURE IN RATS: EFFECT OF CALORIE RESTRICTION (165 PP) The prevalence of obesity around the world has increased in recent years. Obesity results from imbalance between calories in and energy expenditure. Total daily energy expenditure (EE), including resting energy expenditure and non-resting energy expenditure, are critical factors that contribute for individual differences in body weight, and are affected by genetic predisposition. The brain serves to regulate energy balance homeostasis via number of neuroendocrine regulators; one of these is the brain melanocortin system, which includes the melanocortin 4 receptor (MC4R). Melanocortin 4 receptor mutation is one of the few known monogenic causes of obesity in humans. MC4R is also the target of numerous genetic variants that contribute to human obesity. Central MC4R plays a critical role in controlling energy homeostasis, increasing energy expenditure, and decreasing food intake. Here, I investigate the contribution of physical activity and EE to obesity in rats lacking functional MC4R, and test the hypothesis that MC4R signaling underlies differential weight loss during calorie restriction. Although rats lacking functional MC4R did not show lower EE under free-fed conditions, they lost significantly less weight during calorie restriction. During weight loss, adaptive thermogenesis occurs where EE is suppressed beyond what is predicted for the smaller body size. Prolonged food restriction in rats resulted in reduced in daily EE, including resting and non-resting EE. These decreases in EE were significant even when the reductions in body weight and lean mass were taken into account. Similarly, the caloric need for moderate-level treadmill activity was decreased by 50% calorie restriction, as were baseline and activity-related muscle thermogenesis, though the ability to increase muscle thermogenesis above baseline levels was not compromised. When sympathetic nervous system drive was measured by assessing norepinephrine turnover (NETO), 50% calorie restriction was found to decrease NETO in three of the four muscle groups examined, while increasing NETO in white adipose tissue. Central activation of MC4R in the ventromedial hypothalamus stimulated this brain-muscle pathway, enhancing activity EE, and this was not compromised by 50% calorie restriction. These data suggest that suppressed activity EE contributes to adaptive thermogenesis during energy restriction; this may stem from decreased SNS drive to skeletal muscle, increasing locomotor efficiency and reducing skeletal muscle thermogenesis. The capacity to increase activity EE in response to central MC4R activation is retained, however, presenting a potential target for pharmacotherapy intervention.
Colleen Novak (Advisor)
173 p.

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Citations

  • Almundarij, T. (2015). POTENTIAL ROLE OF MELANOCORTIN 4 RECEPTOR IN PHYSICAL ACTIVITY ENERGY EXPENDITURE IN RATS: EFFECT OF CALORIE RESTRICTION [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1448118733

    APA Style (7th edition)

  • Almundarij, Tariq. POTENTIAL ROLE OF MELANOCORTIN 4 RECEPTOR IN PHYSICAL ACTIVITY ENERGY EXPENDITURE IN RATS: EFFECT OF CALORIE RESTRICTION . 2015. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1448118733.

    MLA Style (8th edition)

  • Almundarij, Tariq. "POTENTIAL ROLE OF MELANOCORTIN 4 RECEPTOR IN PHYSICAL ACTIVITY ENERGY EXPENDITURE IN RATS: EFFECT OF CALORIE RESTRICTION ." Doctoral dissertation, Kent State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1448118733

    Chicago Manual of Style (17th edition)