Abstract 19336: Chronic Vagal Nerve Stimulation Causes Weight Loss by Reducing Food Intake and Feeding Efficiency in Mice

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.

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Abstract 512: Anorectic and Thermogenic Effects of Chronic Vagal Nerve Stimulation in Mice

Hypertension ◽

10.1161/hyp.64.suppl_1.512 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Daniel P Dias ◽

Donald A Morgan ◽

Harald M Stauss ◽

Kamal Rahmouni

Keyword(s):

Weight Loss ◽

Body Weight ◽

Oxygen Consumption ◽

Weight Gain ◽

Food Intake ◽

Metabolic Rate ◽

Body Weight Gain ◽

Caloric Intake ◽

Vagal Nerve ◽

Feeding Efficiency

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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SOME PHYSIOLOGICAL AND NUTRITIONAL ASPECTS OF THE DWARF CHICKEN

Canadian Journal of Animal Science ◽

10.4141/cjas71-028 ◽

1971 ◽

Vol 51 (1) ◽

pp. 209-216 ◽

Cited By ~ 6

Author(s):

G. RAJARATNAM ◽

J. D. SUMMERS ◽

A. S. WOOD ◽

E. T. MORAN Jr.

Keyword(s):

Body Weight ◽

Oxygen Consumption ◽

Weight Gain ◽

Body Temperature ◽

Metabolic Rate ◽

Body Weight Gain ◽

Carcass Composition ◽

Lower Body ◽

Brand Name ◽

Dwarf Chicken

A study was undertaken to investigate the feasibility of hypothyroidism as an explanation for the smaller body size and lower metabolic activity of the recessive sex-linked dwarf chicken. A significant increase in body weight gain and feed intake for dwarf chicks with little change in these parameters for normal chicks receiving a diet supplemented with Protamone (brand name for iodinated casein) suggests a hypothyroidic state for the dwarfs. Similarly, a significantly lower body temperature, oxygen consumption and basal metabolic rate with a higher percentage of carcass fat in dwarf chicks as compared with normal ones supports the above hypothesis. Protamone supplementation of the diet increased body temperature and metabolic rate, and altered the carcass composition of the dwarfs to values closer to that of normal chicks, again suggesting a low thyroxine output for the dwarfs.

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Effect of nicotine on body composition in mice

Journal of Endocrinology ◽

10.1530/joe-11-0350 ◽

2011 ◽

Vol 212 (3) ◽

pp. 317-326 ◽

Cited By ~ 32

Author(s):

Michael Mangubat ◽

Kabirullah Lutfy ◽

Martin L Lee ◽

Laura Pulido ◽

David Stout ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Weight Gain ◽

Partial Agonist ◽

Body Weight Gain ◽

Caloric Intake ◽

Fat Distribution ◽

Abdominal Fat ◽

Chow Diet ◽

Fat Composition

Nicotine induces weight loss in both humans and rodents consuming a regular diet; however, the effect of nicotine on body weight and fat composition in rodents consuming a high-fat diet (HFD) has not been well studied. Thus, this study examined the effect of nicotine vs saline on body weight and fat composition in mice fed with either an HFD (62% of kcal from fat) or a standard normal chow diet (NCD) for 7 weeks. Nicotine dose dependently reduced body weight gain in mice that consumed both diets, but this effect was significantly greater in mice on the HFD. Caloric intake was decreased in nicotine-treated mice. Estimates of energy intake suggested that decreased caloric intake accounted for all the reduced weight gain in mice on an NCD and 66% of the reduced weight gain on an HFD. Computed tomography analysis for fat distribution demonstrated that nicotine was effective in reducing abdominal fat in mice that consumed the HFD, with nicotine treatment leading to lower visceral fat. The effect of nicotine on weight loss in mice on an HFD was completely blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor (nAChR) antagonist, but only partially blocked by the α4β2 nAChR partial agonist/antagonist, varenicline. We conclude that nicotine is effective in preventing HFD-induced weight gain and abdominal fat accumulation.

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Feeding and temperature responses to intravenous leptin infusion are differential predictors of obesity in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00508.2002 ◽

2004 ◽

Vol 286 (4) ◽

pp. R756-R763 ◽

Cited By ~ 8

Author(s):

Marie-Pierre Ruffin ◽

Tiziana Adage ◽

Folkert Kuipers ◽

Jan H. Strubbe ◽

Anton J. W. Scheurink ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Body Weight Gain ◽

Caloric Intake ◽

High Energy ◽

Leptin Resistance ◽

Variable Effect ◽

Male Wistar Rats ◽

Plasma Leptin

Obesity is frequently associated with leptin resistance. The present study investigated whether leptin resistance in rats is present before obesity develops, and thus could underlie obesity induced by 16 wk exposure to a liquid, palatable, high-energy diet (HED). Before HED exposure, male Wistar rats (weighing between 330 and 360 g) received intravenous infusions of 20 μg leptin 2 h before dark (∼57 μg/kg rat). Relative to saline infusion, this caused a highly variable effect on food intake (ranging between -94 and +129%), with food intake suppression that appeared negatively correlated with HED-induced increases in body weight gain, caloric intake, adiposity, and plasma leptin levels. In contrast, leptin's thermogenic response was positively correlated to body weight gain linked to weights of viscera, but not to adiposity. Before HED exposure, leptin unexpectedly increased food intake in some rats (fi+, n = 8), whereas others displayed the normal reduction in food intake (fi-, n = 7). HED-exposed fi+ rats had higher plasma leptin levels, retroperitoneal fat pad weight, HED intake, and body weight gain than fi- and chow-fed rats. These parameters were also higher in HED-exposed fi- rats relative to chow rats, except for plasma leptin concentrations. It is concluded that leptin's reduced efficacy to suppress food intake could predict obesity on an HED. An unexpected orexigenic effect of leptin might potentially contribute to this as well.

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Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00358.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. E29-E37 ◽

Cited By ~ 3

Author(s):

Mariana Peduti Halah ◽

Paula Beatriz Marangon ◽

Jose Antunes-Rodrigues ◽

Lucila L. K. Elias

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Food Intake ◽

White Adipose Tissue ◽

Energy Homeostasis ◽

Body Weight Gain ◽

Adult Life ◽

Male Rats ◽

Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

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The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice

Endocrinology ◽

10.1210/en.2019-00408 ◽

2019 ◽

Vol 160 (10) ◽

pp. 2441-2452 ◽

Cited By ~ 15

Author(s):

Tomokazu Hata ◽

Noriyuki Miyata ◽

Shu Takakura ◽

Kazufumi Yoshihara ◽

Yasunari Asano ◽

...

Keyword(s):

Body Weight ◽

Anorexia Nervosa ◽

Weight Gain ◽

Food Intake ◽

Brain Stem ◽

Body Weight Gain ◽

Field Tests ◽

Compulsive Behavior ◽

The Brain ◽

Poor Weight Gain

Abstract Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.

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Bimatoprost promotes satiety and attenuates body weight in rats fed standard or obesity-promoting diets.

10.21203/rs.3.rs-24991/v1 ◽

2020 ◽

Author(s):

Clayton Spada ◽

Chau Vu ◽

Iona Raymond ◽

Warren Tong ◽

Chia-Lin Chuang ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Gastric Emptying ◽

Food Intake ◽

Visceral Fat ◽

Body Weight Gain ◽

Metabolic Effects ◽

Sprague Dawley ◽

Hormone Levels ◽

Gut Hormone

Abstract Background Bimatoprost negatively regulates adipogenesis in vitro and likely participates in a negative feedback loop on anandamide-induced adipogenesis. Here, we investigate the broader metabolic effects of bimatoprost action in vivo in rats under both normal state and obesity-inducing conditions. Methods Male Sprague Dawley rats were a fed standard chow (SC) diet in conjunction with dermally applied bimatoprost treatment for a period of 9–10 weeks. Body weight gain, energy expenditure, food intake, and hormones associated with satiety were measured. Gastric emptying was also separately evaluated. In obesity-promoting diet studies, rats were fed a cafeteria diet (CAF) and gross weight, fat accumulation in SQ, visceral fat and liver was evaluated together with standard serum chemistry. Results Chronic bimatoprost administration attenuated weight gain in rats fed either standard or obesity-promoting diets over a 9–10 weeks. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Additionally, SQ and visceral fat mass was distinctly affected by treatment. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Conclusions These findings suggest that bimatoprost (and possibly prostamide F2α) regulates energy homeostasis through actions on dietary intake. These actions likely counteract the metabolic actions of anandamide through the endocannabinoid system potentially revealing a new pathway that could be exploited for therapeutic development.

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Oxytocin Administration Alleviates Acute but Not Chronic Leptin Resistance of Diet-Induced Obese Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20010088 ◽

2018 ◽

Vol 20 (1) ◽

pp. 88 ◽

Cited By ~ 4

Author(s):

Mehdi Labyb ◽

Chloé Chrétien ◽

Aurélie Caillon ◽

Françoise Rohner-Jeanrenaud ◽

Jordi Altirriba

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Body Weight Gain ◽

Leptin Resistance ◽

Obese Mice ◽

Short Term ◽

Continuous Administration ◽

Pre Treatment ◽

Treatment Of Obesity

Whereas leptin administration only has a negligible effect on the treatment of obesity, it has been demonstrated that its action can be improved by co-administration of leptin and one of its sensitizers. Considering that oxytocin treatment decreases body weight in obese animals and humans, we investigated the effects of oxytocin and leptin cotreatment. First, lean and diet-induced obese (DIO) mice were treated with oxytocin for 2 weeks and we measured the acute leptin response. Second, DIO mice were treated for 2 weeks with saline, oxytocin (50 μg/day), leptin (20 or 40 µg/day) or oxytocin plus leptin. Oxytocin pre-treatment restored a normal acute leptin response, decreasing food intake and body weight gain. Chronic continuous administration of oxytocin or leptin at 40 µg/day decreased body weight in the presence (leptin) or in the absence (oxytocin) of cumulative differences in food intake. Saline or leptin treatment at 20 µg/day had no impact on body weight. Oxytocin and leptin cotreatments had no additional effects compared with single treatments. These results point to the fact that chronic oxytocin treatment improves the acute, but not the chronic leptin response, suggesting that this treatment could be used to improve the short-term satiety effect of leptin.

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Effects of Consuming Sugar-Sweetened Beverages for 2 Weeks on 24-h Circulating Leptin Profiles, Ad Libitum Food Intake and Body Weight in Young Adults

Nutrients ◽

10.3390/nu12123893 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3893 ◽

Cited By ~ 1

Author(s):

Desiree M. Sigala ◽

Adrianne M. Widaman ◽

Bettina Hieronimus ◽

Marinelle V. Nunez ◽

Vivien Lee ◽

...

Keyword(s):

Young Adults ◽

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Energy Intake ◽

Body Weight Gain ◽

Energy Requirement ◽

Area Under The Curve ◽

Sugar Sweetened Beverage ◽

Ad Libitum

Sugar-sweetened beverage (sugar-SB) consumption is associated with body weight gain. We investigated whether the changes of (Δ) circulating leptin contribute to weight gain and ad libitum food intake in young adults consuming sugar-SB for two weeks. In a parallel, double-blinded, intervention study, participants (n = 131; BMI 18–35 kg/m2; 18–40 years) consumed three beverages/day containing aspartame or 25% energy requirement as glucose, fructose, high fructose corn syrup (HFCS) or sucrose (n = 23–28/group). Body weight, ad libitum food intake and 24-h leptin area under the curve (AUC) were assessed at Week 0 and at the end of Week 2. The Δbody weight was not different among groups (p = 0.092), but the increases in subjects consuming HFCS- (p = 0.0008) and glucose-SB (p = 0.018) were significant compared with Week 0. Subjects consuming sucrose- (+14%, p < 0.0015), fructose- (+9%, p = 0.015) and HFCS-SB (+8%, p = 0.017) increased energy intake during the ad libitum food intake trial compared with subjects consuming aspartame-SB (−4%, p = 0.0037, effect of SB). Fructose-SB decreased (−14 ng/mL × 24 h, p = 0.0006) and sucrose-SB increased (+25 ng/mL × 24 h, p = 0.025 vs. Week 0; p = 0.0008 vs. fructose-SB) 24-h leptin AUC. The Δad libitum food intake and Δbody weight were not influenced by circulating leptin in young adults consuming sugar-SB for 2 weeks. Studies are needed to determine the mechanisms mediating increased energy intake in subjects consuming sugar-SB.

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