Faculty Opinions recommendation of Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake.

Author(s):  
L. Alison McInnes
1984 ◽  
Vol 247 (5) ◽  
pp. R837-R841 ◽  
Author(s):  
K. J. Nilssen ◽  
J. A. Sundsfjord ◽  
A. S. Blix

Food intake, body weight, serum levels of triiodothyronine (T3) and free thyroxine (FT4), and metabolic rate were measured at intervals in Svalbard (SR) and Norwegian (NR) reindeer. From summer to winter food intake decreased 57 (SR) and 55% (NR), while body weight decreased 8.6 (SR) and 3.8% (NR). In SR T3 and FT4 changed seasonally, whereas this was only evident for T3 in NR. Resting (standing) metabolic rate (RMR) in winter was 1.55 (SR) and 2.05 W X kg-1 (NR), lower critical temperature (TLC) being -50 (SR) and -30 degrees C (NR). RMR in summer was 2.15 (SR) and 2.95 W X kg-1 (NR), TLC being -15 (SR) and 0 degrees C (NR). Seasonal changes in T3 and FT4 did not coincide with changes in food intake or RMR in either SR or NR. RMR did, however, correlate with food intake. This indicates that seasonal changes in RMR are due to the thermic effects of feeding and represent no physiological adaptation aimed at conservation of energy during winter.


Neuropeptides ◽  
2017 ◽  
Vol 62 ◽  
pp. 37-43 ◽  
Author(s):  
Lindy Sergeant ◽  
Carla Rodriguez-Dimitrescu ◽  
Christopher C. Barney ◽  
Gregory S. Fraley

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Harald M Stauss ◽  
Daniel P Dias ◽  
Donald A Morgan ◽  
Kamal Rahmouni

Chronic electrical vagal nerve stimulation (VNS) has emerged as a new tool to treat human diseases including obesity. Indeed, chronic VNS has been shown to cause weight loss in humans and in experimental animal models. However, the mechanisms for VNS-induced weight loss are largely unknown. We hypothesized that an increase in metabolic rate together with reduced caloric intake and reduced feeding efficiency (body weight gain per calories consumed) contribute to chronic VNS-induced weight loss or reduced weight gain. To test this hypothesis, we developed a miniaturized microprocessor-operated nerve stimulator for chronic use in conscious mice. Effectiveness of the stimulator was verified by bradycardia at stimulation frequencies above 5 Hz (3V, 1mA, 1ms pulses). Male C57Bl/6 mice (16 weeks old, standard mouse chow diet) were instrumented with nerve stimulators (3V, 1mA, 1ms pulses at 5 Hz) on the right cervical vagal nerve and body weight, food intake and metabolic rate (indirect calorimetry) were determined at baseline and weekly thereafter. After the initial post-surgical weight loss, sham animals (n=9, stimulators off) regained pre-surgical body weight within 16 days (100.0±2.7%). In contrast, mice with chronic VNS (n=12) never reestablished pre-surgical body weight (94.5±0.9% on day 16, P<0.05 vs. sham). Caloric intake was significantly reduced in mice with chronic VNS compared to sham animals (74.7±2.4 vs. 84.6±4.2 kcal/week, P<0.05). Likewise, mice with chronic VNS showed significantly reduced feeding efficiency compared to sham mice (2.6±2.0 vs. 10.6±2.4 mg body weight gain per kcal consumed). Oxygen consumption tended to be elevated (2734±152 vs. 2490±124 mL/kg/h, P=0.23) during the first week, but not thereafter. In conclusion reduced food intake and lower feeding efficiency contribute to reduced weight gain in mice with chronic VNS. We speculate that an initial increase in metabolic rate (assessed by oxygen consumption) may be antagonized by compensatory mechanisms in response to chronic VNS.


2012 ◽  
Vol 302 (7) ◽  
pp. E759-E767 ◽  
Author(s):  
Elinor L. Sullivan ◽  
Jean Shearin ◽  
Frank H. Koegler ◽  
Judy L. Cameron

The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone ( P < 0.0001) and follicle-stimulating hormone levels ( P < 0.0001), consistent with the estrogenic action of the compound. GSK232802A treatment produced a small but sustained weight loss (4.6 ± 1.0%, P < 0.0001) and reduced adiposity ( P < 0.0001), which was due at least in part to a suppression of food intake (3.6 ± 3.7%, P < 0.0001). Physical activity increased during the 3rd mo of treatment ( P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment ( P = 0.02). Metabolic rate did not change ( P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.


2009 ◽  
Vol 297 (2) ◽  
pp. E545-E551 ◽  
Author(s):  
David A. Bechtold ◽  
Tina R. Ivanov ◽  
Simon M. Luckman

Neuromedin U (NMU) is known to have potent actions on appetite and energy expenditure. Deletion of the NMU gene in mice leads to an obese phenotype, characterized by hyperphagia and decreased energy expenditure. Conversely, transgenic mice that overexpress proNMU exhibit reduced body weight and fat storage. Here, we show that central administration of NMU or the related peptide neuromedin S (NMS) dose-dependently decreases food intake, increases metabolic rate, and leads to significant weight loss in mice. The effects of NMU and NMS on both feeding and metabolism are almost completely lost in mice lacking the putative CNS receptor for NMU and NMS, NMUr2. However, NMUr2 knockout mice do not exhibit overt differences in body weight or energy expenditure compared with wild-type mice, suggesting that the dramatic phenotype of the NMU gene knockout mouse is not due simply to the loss of NMU/NMUr2 signaling. Putative proteolytic cleavage sites indicate that an additional peptide is produced from the NMU precursor protein, which is extremely well conserved between human, mouse, and rat. Here, we demonstrate that this peptide, proNMU104-136, has a pronounced effect on energy balance in mice. Specifically, central administration of proNMU104-136 causes a significant but transient (∼4 h) increase in feeding, yet both food intake and body weight are decreased over the following 24 h. proNMU104-136 administration also significantly increased metabolic rate. These results suggest that proNMU104-136 is a novel modulator of energy balance and may contribute to the phenotype exhibited by NMU knockout mice.


2007 ◽  
Vol 293 (3) ◽  
pp. R992-R1002 ◽  
Author(s):  
ChuanFeng Wang ◽  
Eric Bomberg ◽  
Charles Billington ◽  
Allen Levine ◽  
Catherine M. Kotz

Brain-derived neurotrophic factor (BDNF) decreases food intake and body weight, but few central sites of action have been identified. The hypothalamic paraventricular nucleus (PVN) is important in energy metabolism regulation, and expresses both BDNF and its receptor. We tested three hypotheses: 1) PVN BDNF reduces feeding and increases energy expenditure (EE), 2) PVN BDNF-enhanced thermogenesis results from increased spontaneous physical activity (SPA) and resting metabolic rate (RMR), and 3) PVN BDNF thermogenic effects are mediated, in part, by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). BDNF (0.5 μg) was injected into the PVN of Sprague-Dawley rats; and oxygen consumption, carbon dioxide production, food intake, and SPA were measured for 24 h in an indirect calorimeter. SPA was also measured in open-field activity chambers for 48 h after BDNF injection. Animals were killed 6 or 24 h after BDNF injection, and BAT UCP1 gene expression was measured with quantitative real-time PCR. BDNF significantly decreased food intake and body weight gain 24 h after injection. Heat production and RMR were significantly elevated for 7 h immediately after BDNF injection. BDNF had no effect on SPA, but increased UCP1 gene expression in BAT at 6 h, but not 24 h after injection. In conclusion, PVN BDNF reduces body weight by decreasing food intake and increasing EE consequent to increased RMR, which may be due, in part, to BAT UCP1 activity. These data suggest that the PVN is an important site of BDNF action to influence energy balance.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Daniel P Dias ◽  
Donald A Morgan ◽  
Harald M Stauss ◽  
Kamal Rahmouni

Electrical vagal nerve stimulation (VNS) has emerged as a new tool to treat human diseases including obesity. Indeed, chronic VNS has been shown to cause weight loss in humans and in experimental animal models. However, the mechanisms by which chronic VNS causes weight loss are largely unknown due in part to the unavailability of implantable nerve stimulators for mice excluding the use of genetically engineered mouse models to investigate these mechanisms. Identification such mechanisms promises to identify novel approaches for weight loss. Here, we report the development of a miniaturized microprocessor-operated nerve stimulator for chronic use in conscious mice. Effectiveness of the stimulator was verified by the bradycardia induced at stimulation frequencies above 5 Hz (3V, 1mA, 1ms pulses). Next, we used the stimulator to test whether changes in metabolic rate, caloric intake and feeding efficiency (body weight gain per calories consumed) contribute to chronic VNS-induced weight loss. Male C57Bl/6 mice (16 weeks old, on standard mouse chow diet) were instrumented with nerve stimulators (3V, 1mA, 1ms pulses at 5 Hz) on the right cervical vagal nerve and body weight, food intake and metabolic rate (indirect calorimetry) were determined at baseline and weekly thereafter. After the initial post-surgical weight loss, sham animals (n=9, stimulators off) regained pre-surgical body weight within 16 days (100.0±2.7%). In contrast, mice with chronic VNS (n=12) never re-established pre-surgical body weight (94.5±0.9% on day 16, P<0.05 vs. sham). Caloric intake was significantly reduced in mice with chronic VNS compared to sham group (74.7±2.4 vs. 84.6±4.2 kcal/week, P<0.05). Likewise, mice with chronic VNS showed significantly reduced feeding efficiency compared to sham mice (2.6±2.0 vs. 10.6±2.4 mg body weight gain per kcal consumed). Oxygen consumption tended to be elevated (2734±152 vs. 2490±124 mL/kg/h) during the first week, but not thereafter. In conclusion, reduced food intake and lower feeding efficiency contribute to VNS-induced weight loss in mice. We speculate that an initial increase in metabolic rate (assessed by oxygen consumption) may be antagonized by compensatory mechanisms triggered by chronic VNS.


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