Human Plasma Ghrelin Levels Increase during a One-Year Exercise Program

Weight loss resulting from decreased caloric intake raises levels of the orexigenic hormone, ghrelin. Because ingested nutrients suppress ghrelin, increased ghrelin levels in hypophagic weight loss may result from decreased inhibitory input by ingested food, rather than from lost weight. We assessed whether ghrelin levels increase in response to exercise-induced weight loss without decreased caloric intake. We randomized 173 sedentary, overweight, postmenopausal women to an aerobic exercise intervention or stretching control group. At baseline, 3 months, and 12 months, we measured body weight and composition, food intake, cardiopulmonary fitness (maximal oxygen consumption), leptin, insulin, and ghrelin. Complete data were available for 168 women (97%) at 12 months. Exercisers lost 1.4 ± 0.4 kg (P < 0.05 compared with baseline; P = 0.01 compared with stretchers) and manifested a significant, progressive increase in ghrelin levels, whereas neither measure changed among stretchers. Ghrelin increased 18% in exercisers who lost more than 3 kg (P < 0.001). There was no change in caloric intake in either group and no effect on ghrelin of exercise per se independent of its impact on body weight. In summary, ghrelin levels increase with weight loss achieved without reduced food intake, consistent with a role for ghrelin in the adaptive response constraining weight loss and, thus, in long-term body weight regulation.

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PO-271 Effects of accumulated exercise with different intensities on insulin resistance in mice

Exercise Biochemistry Review ◽

10.14428/ebr.v1i5.11203 ◽

2018 ◽

Vol 1 (5) ◽

Author(s):

Yuli Zhang ◽

Songtao Wang ◽

Fei Liang ◽

Xiangyu Shuai ◽

Weibao Liang ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

High Intensity ◽

Exercise Intervention ◽

Exercise Program ◽

Exercise Group ◽

The Body ◽

Moderate Intensity ◽

Control Group ◽

Continuous Exercise

Objective The aim of this study was to investigate the effect of 8-week moderate-intensity and high-intensity accumulated exercise on insulin resistance in mice, compared with the moderate intensity continuous exercise with equal workload, which will provide an experimental reference for seeking a more reasonable and effective exercise program to break sedentary behavior and improve metabolic diseases such as IR. Methods Eighty 4-week-old C57BL/6J mice were randomly divided into normal diet group (group C) and high-fat diet group (group H), fed with different diet. At the 10th weekend, insulin resistance model was judged by OGTT curve (AUC) and fasting blood glucose. All mice with insulin resistance were randomly divided into four groups: IR control group (IC), IR moderate-intensity continuous exercise group (IE), IR moderate-intensity accumulated exercise group (IM), IR high-intensity accumulated exercise group (IH), retained normal diet control group (C), with 12 mice for each group. All groups were fed with normal feed. The three exercise-related group performed an 8-week’s treadmill exercise program with equal workload (involve preparation and relaxation activities,0°platform slope, 5 days/week). For IE group, mice run 50min continuously with the velocity of 11m/min. For IM group，mice exercised 12.5 min per session, total 4 sessions per day, with 3-hour’s interval and the velocity of 11m/min. The IH group performed an alike exercise program with IM group, except the running speed (19m/min) and exercise time (7.5min). On the 8th weekend of exercise, FBG, OCTT, FINS, HOME- IR, and ISI were tested for each groups. Results 1. Compared with group C, body weight, FBG and OGTT-AUC were significantly increased in group H (P<0.05 or P<0.01). 76% mice were induced to insulin resistance successfully. 2. Before and after exercise intervention of 8 weeks, there were no significant changes in body weight and OGTT-AUC, while the FBG was significantly increased in IC group (P<0.05). Body weight, FBG, and OGTT-AUC significantly decreased in IE group, IM group and IH group (P<0.05 or P<0.01). 3. After 8 weeks of exercise intervention, the FBG in the IE group, IM group, and IH group were significantly lower than that in C group (P<0.05 or P<0.01). Compared with the IC group, the FBG, FINS, OGTT-AUC, and HOME-IR in IM group, IH group and IE group were lower than those in the IC group (P<0.05 or P<0.01). Compared with the IE group, the body weight and HOME-IR index of IH group were significantly lower than those in IE group (P<0.01). Compared with IH group, the HOME-IR in IH group was lower than that in IM group (P<0.05); There was no significant difference between IM group and IE group. Conclusions 1. Chronic moderate-intensity continuous exercise, moderate-intensity accumulated exercise, and high-intensity accumulated exercise all can effectively improve the glucose metabolism and insulin resistance in IR mice. 2.Compared with moderate-intensity accumulated exercise and moderate-intensity continuous exercise, the high-intensity accumulated exercise with equal workload is more effective in reducing the body weight and improving insulin resistance in IR mice.

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

Circulation ◽

10.1161/circ.130.suppl_2.19336 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Harald M Stauss ◽

Daniel P Dias ◽

Donald A Morgan ◽

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

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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Novel α-MSH analog causes weight loss in obese rats and minipigs and improves insulin sensitivity

Journal of Endocrinology ◽

10.1530/joe-13-0284 ◽

2013 ◽

Vol 220 (2) ◽

pp. 97-107 ◽

Cited By ~ 10

Author(s):

Keld Fosgerau ◽

Kirsten Raun ◽

Cecilia Nilsson ◽

Kirsten Dahl ◽

Birgitte S Wulff

Keyword(s):

Weight Loss ◽

Body Weight ◽

Insulin Sensitivity ◽

Food Intake ◽

Body Weight Loss ◽

Vehicle Control ◽

Glucose Disposal ◽

Control Group ◽

Euglycemic Hyperinsulinemic Clamp ◽

Peptide Agonist

Obesity is a major burden to people and to health care systems around the world. The aim of the study was to characterize the effect of a novel selective α-MSH analog on obesity and insulin sensitivity. The subchronic effects of the selective MC4-R peptide agonist MC4-NN1-0182 were investigated in diet-induced obese (DIO) rats and DIO minipigs by assessing the effects on food intake, energy consumption, and body weight. The acute effect of MC4-NN1-0182 on insulin sensitivity was assessed by a euglycemic–hyperinsulinemic clamp study in normal rats. Three weeks of treatment of DIO rats with MC4-NN1-0182 caused a decrease in food intake and a significant decrease in body weight 7±1%,P<0.05 compared with 3±1% increase with the vehicle control. In DIO minipigs, 8 weeks of treatment with MC4-NN1-0182 resulted in a body weight loss of 13.3±2.5 kg (13±3%), whereas the vehicle control group had gained 3.7±1.4 kg (4±1%). Finally, clamp studies in normal rats showed that acute treatment with MC4-NN1-0182 caused a significant increase in glucose disposal (Rd) compared with vehicle control (Rd, mg/kg per min, 17.0±0.7 vs 13.9±0.6,P<0.01). We demonstrate that treatment of DIO rats or minipigs with a selective MC4-R peptide agonist causes weight loss. Moreover, we have demonstrated weight-independent effects on insulin sensitivity. Our observations identify MC4 agonism as a viable target for the treatment of obesity and insulin resistance.

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The Rat's Adjustment to 23-, 47-, and 71-Hour Food-Deprivation Schedules

Psychological Reports ◽

10.2466/pr0.1964.14.3.663 ◽

1964 ◽

Vol 14 (3) ◽

pp. 663-669 ◽

Cited By ~ 8

Author(s):

Robert H. Dufort

Keyword(s):

Weight Loss ◽

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Food Deprivation ◽

Control Group ◽

Severe Weight Loss

In this experiment the adjustment of rats to three schedules of food deprivation was studied. Groups of Ss were placed on either 23-hr., 47-hr., or 71-hr. food-deprivation schedules for a period of 18 days. A fourth, non-deprived control group was also employed. The measures of adjustment used were body weight, and weight gain and food intake during the time food was available. The results showed that, as expected from previous research, Ss on the 23-hr. schedule were in the process of adjusting to the schedule at the end of 18 days. Ss on the 47-hr. and 71-hr. schedules, however, experienced severe weight loss and were not able to adjust to their schedules.

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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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OP0159 EFFICACY OF COMPREHENSIVE TECHNOLOGY-ASSISTED HOME-BASED EXERCISE IN ANKYLOSING SPONDYLITIS: A RANDOMIZED, CONTROLLED TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5100 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 100.3-100

Author(s):

Y. Wang ◽

X. Liu ◽

Y. Shi ◽

X. Ji ◽

W. Wang ◽

...

Keyword(s):

Exercise Intervention ◽

Medical Center ◽

Controlled Trial ◽

Intervention Group ◽

Exercise Program ◽

Group Differences ◽

Control Group ◽

Home Based ◽

The Mean

Background:Clinical practice guidelines recommend that exercise is an essential component in the self-management of Ankylosing Spondylitis (AS). Attending supervised interventions requiring periodic medical center visits can be burdensome and patients may decline participation, whereas, effective home-based exercise interventions that do not need regular medical center visits are likely to be more accessible and acceptable for patients with AS. Recently, increasing evidences have been accumulated that the wearable devices could facilitate patients with inflammatory arthritis by giving exercise instructions and improving self-efficacy. Therefore, patients with AS may benefit from an effective technology-assisted home-based exercise intervention.Objectives:To investigate the efficacy of a comprehensive technology-assisted home-based exercise intervention on disease activity in patients with AS.Methods:This study was a 16-week assessor-blinded, randomized, waiting-list controlled trial (ChiCTR1900024244). Patients with AS were randomly allocated to the home-based exercise intervention group and the waiting-list control group. A 16-week comprehensive exercise program consisting of a moderate intensity (64%-76% HRmax) aerobic training for 30min on 5 days/week and a functional training for 60min on 3 days/week was given to patients in the intervention group immediately after randomization, with 1.5h training sessions for two consecutive days by a study physical therapist at baseline and Week 8. The aerobic exercise intensity was controlled by a Mio FUSE Wristband with a smartphone application. The functional training consisted of the posture training, range of motion exercises, strength training, stability training and stretching exercises. Patients in control group received standard care during the 16-week follow-up and started to receive the exercise program at Week 16. The primary outcome was ASDAS at Week 16. The secondary outcomes were BASDAI, BASFI, BASMI, ASAS HI, peak oxygen uptake, body composition and muscle endurance tests. The mean difference between groups in change from baseline was analyzed with the analysis of covariance.Results:A total of 54 patients with AS were enrolled (26 in intervention group and 28 in control group) and 46 (85.2%) patients completed the 16-week follow-up. The mean difference of ASDAS between groups in change from baseline to 16-week follow-up was −0.2 (95% CI, −0.4 to 0.003, P = 0.032), and the mean change from baseline was -0.4 (95% CI, -0.5 to -0.2) in the intervention group vs -0.1 (95% CI, -0.3 to 0.01) in the control group, respectively. Significant between-group differences were found between groups for BASDAI (−0.5 [95% CI, −0.9 to −0.2], P = 0.004), BASMI (−0.7 [95% CI, −1.1 to −0.4], P <0.001), BASFI (−0.3 [95% CI, −0.6 to 0.01], P=0.035), peak oxygen uptake (2.7 [95% CI, 0.02 to 5.3] ml/kg/min, P=0.048) and extensor endurance test (17.8 [95% CI, 0.5 to 35.2]s, P=0.044) at Week 16. Between-group differences were detected in ASAS HI (−0.9 [95% CI, −1.7 to −0.1], P=0.030), body fat percentage (−1.0 [95% CI, −2.0 to −0.01] %, P=0.048) and visceral adipose tissue (−4.9 [95% CI, −8.5 to −1.4] cm2, P=0.008) at Week 8, but not at Week 16. No significant between-group differences were detected in the total lean mass, time up and go test and the flexor endurance test during the follow-up.Conclusion:Comprehensive technology-assisted home-based exercise has been shown to have beneficial effects on disease activity, physical function, spinal mobility, aerobic capacity, and body composition as well as in improving fatigue and morning stiffness of patients with AS.References:[1]van der Heijde D, Ramiro S, Landewé R, et al. Ann Rheum Dis 2017;76:978–991.Disclosure of Interests:None declared

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GPR40 reduces food intake and body weight through GLP-1

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00435.2016 ◽

2017 ◽

Vol 313 (1) ◽

pp. E37-E47 ◽

Cited By ~ 16

Author(s):

Judith N. Gorski ◽

Michele J. Pachanski ◽

Joel Mane ◽

Christopher W. Plummer ◽

Sarah Souza ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Food Intake ◽

Partial Agonist ◽

Glucose Lowering ◽

Partial Agonists ◽

Lower Glucose ◽

Glucagon Like Peptide 1 ◽

Glucose Stimulated Insulin Secretion ◽

G Protein Coupled

G protein-coupled receptor 40 (GPR40) partial agonists lower glucose through the potentiation of glucose-stimulated insulin secretion, which is believed to provide significant glucose lowering without the weight gain or hypoglycemic risk associated with exogenous insulin or glucose-independent insulin secretagogues. The class of small-molecule GPR40 modulators, known as AgoPAMs (agonist also capable of acting as positive allosteric modulators), differentiate from partial agonists, binding to a distinct site and functioning as full agonists to stimulate the secretion of both insulin and glucagon-like peptide-1 (GLP-1). Here we show that GPR40 AgoPAMs significantly increase active GLP-1 levels and reduce acute and chronic food intake and body weight in diet-induced obese (DIO) mice. These effects of AgoPAM treatment on food intake are novel and required both GPR40 and GLP-1 receptor signaling pathways, as demonstrated in GPR40 and GLP-1 receptor-null mice. Furthermore, weight loss associated with GPR40 AgoPAMs was accompanied by a significant reduction in gastric motility in these DIO mice. Chronic treatment with a GPR40 AgoPAM, in combination with a dipeptidyl peptidase IV inhibitor, synergistically decreased food intake and body weight in the mouse. The effect of GPR40 AgoPAMs on GLP-1 secretion was recapitulated in lean, healthy rhesus macaque demonstrating that the putative mechanism mediating weight loss translates to higher species. Together, our data indicate effects of AgoPAMs that go beyond glucose lowering previously observed with GPR40 partial agonist treatment with additional potential for weight loss.

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Effects of the lipase inhibitor orlistat on intake and preference for dietary fat in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.271.1.r48 ◽

1996 ◽

Vol 271 (1) ◽

pp. R48-R54 ◽

Cited By ~ 2

Author(s):

K. Ackroff ◽

A. Sclafani

Keyword(s):

Body Weight ◽

Dietary Fat ◽

Body Weight Gain ◽

Caloric Intake ◽

Female Rats ◽

Control Group ◽

Fat Intake ◽

Fat Absorption ◽

Drug Induced ◽

Dietary Fat Intake

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.

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Protein appetite is increased after central leptin-induced fat depletion

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00322.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. R1468-R1473 ◽

Cited By ~ 3

Author(s):

Michael F. Wiater ◽

Bryan D. Hudson ◽

Yvette Virgin ◽

Sue Ritter

Keyword(s):

Body Weight ◽

Food Intake ◽

Body Fat ◽

Caloric Intake ◽

Sprague Dawley ◽

Body Protein ◽

Macronutrient Selection ◽

Daily Diet ◽

Nadir Point ◽

And Control

Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed, and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fat-depleted nadir, while food intake returns to normal caloric levels, presumably in defense of energy and nutritional homeostasis. This model of leptin treatment offers the opportunity to examine controls of food intake that are independent of leptin's actions, and provides a window for examining the nature of feeding controls in a “fatless” animal. Here we evaluate macronutrient selection during this fat-depleted phase of leptin treatment. Adult, male Sprague-Dawley rats were maintained on standard pelleted rodent chow and given daily lateral ventricular injections of leptin or vehicle solution until body weight reached the nadir point and food intake returned to normal levels. Injections were then continued for 8 days, during which rats self-selected their daily diet from separate sources of carbohydrate, protein, and fat. Macronutrient choice differed profoundly in leptin and control rats. Leptin rats exhibited a dramatic increase in protein intake, whereas controls exhibited a strong carbohydrate preference. Fat intake did not differ between groups at any time during the 8-day test. Despite these dramatic differences in macronutrient selection, total daily caloric intake did not differ between groups except on day 2. Thus controls of food intake related to ongoing metabolic and nutritional requirements may supersede the negative feedback signals related to body fat stores.

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