Differential Effects of Intracerebroventricular Glucagon-Like Peptide-1 on Feeding and Energy Expenditure Regulation

Hwa, Joyce; Ghibaudi, Lorraine; Williams, Patricia Ana María; Witten, Melanie; Tedesco, R; Strader, Catherine D.

doi:10.1016/s0196-9781(98)00033-3

Cited by 55 publications

(46 citation statements)

References 20 publications

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“…It seems that the effect on carbohydrate metabolism is greatest during the ®rst hour of the infusion, while the fat metabolism is affected most during the last 2 h (120 ± 240 min), presumably re¯ecting the nature and timing of lipid absorption and metabolic pathways. 44 ± 46 Our ®nding of a decreased diet-induced thermogenesis at ®rst sight contrasts with the results of Hwa 27 and Shalev. 28 Hwa used rats and i.c.v.…”

Section: Discussioncontrasting

confidence: 69%

“…infusion of GLP-1 resulted in an increased O 2 consumption in lean rats while it was unchanged in obese animals. 27 Shalev and co-workers observed an increased resting energy expenditure during peripheral GLP-1 administration in humans during a hyperglycaemic clamp, 28 presumably due to the stimulation of insulin release. How GLP-1 administration during and after a meal affects energy expenditure in humans is still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…26 The effect of GLP-1 on energy expenditure, representing the other side of the energy balance equation, has only been investigated in one animal and one human study. 27,28 In rats a single i.c.v. infusion of GLP-1 resulted in an increased O 2 consumption in lean rats while it was unchanged in obese animals.…”

Section: Introductionmentioning

confidence: 99%

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The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans

Flint¹,

Raben²,

et al. 2000

Int J Obes

108

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OBJECTIVE: To investigate the effects of a near-physiological peripheral glucagon-like peptide-1 (GLP-1) infusion, during and after a breakfast of ®xed energy content, on resting energy expenditure, substrate oxidation and metabolism and the desire to eat speci®c types of food in humans. DESIGN: A placebo-controlled, randomized, blinded, cross-over study. Infusion (GLP-1, 50 pmolakg Â h or saline) was started simultaneously with initiation of the test meals. SUBJECTS: 20 healthy, normal weight (body mass index 20.3 ± 25.7 kgam 2 ) men of 20 ± 31 y of age. MEASUREMENTS: Energy expenditure and substrate oxidations were measured before and for 4 h after standard breakfast (20% of calculated daily energy requirements, 50% of energy from carbohydrates, 37% of energy from fat and 13% of energy from protein) using a ventilated hood system. Visual analogue scales were used throughout the experiment to assess the desire to eat speci®c types of food and the palatability of the test meals. Blood was sampled throughout the day for analysis of plasma hormone and substrate concentrations. RESULTS: Diet-induced thermogenesis (DIT) was lower (47%) on the GLP-1 infusion than on the saline infusion (P`0.0001). This was due to a lower carbohydrate oxidation (P`0.01). No differences in fat oxidation or total 4 h protein oxidation were observed. All hormone and substrate pro®les except non-esteri®ed fatty acids (NEFA) and cholecystokinin (CCK) were signi®cantly suppressed (GLP-2 completely suppressed) during the GLP-1 infusion, whereas pro®les of NEFA and CCK differed in time course during the two treatments (treatment Â time effect), P`0.0001). GLP-1 infusion also suppressed the desire to eat all food types following the breakfast (treatment effect: P`0.05). CONCLUSION: Peripheral GLP-1 decreased DIT and carbohydrate oxidation, probably secondary to a delayed absorption of nutrients, since substrate and hormone concentrations in plasma were suppressed during GLP-1 infusion. Endogenous secretion of GLP-1 and GLP-2 was completely suppressed by GLP-1 infusion. Finally, the desire to eat any type of food was decreased by exogenous administrated GLP-1.

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Section: Discussioncontrasting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

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The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans

Flint¹,

Raben²,

et al. 2000

Int J Obes

108

View full text Add to dashboard Cite

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“…Exactly the same time was spent on the two test days for each individual subject. Postprandial resting metabolic rate was measured for 4 h, and blood samples were taken 15,30,45,60,90,120,150,180,210,240 and 270 min after the start of the breakfast and again after the ad libitum lunch, served at 2:15 pm (300 min). Ratings of subjective sensations were made on 100 mm visual analogue scales (VAS) with the text expressing the most positive and the most negative rating anchored at each end.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…infusion of GLP-1 resulted in an increased O 2 consumption in lean animals while it was unchanged in obese animals. 15 In normal-weight human subjects the effect of exogenous peripheral infusions of GLP-1 during and after meal intake on O 2 consumption seems to parallel the retarded absorption and processing of nutrients. 16,17 However, the effect of i.v.…”

Section: Introductionmentioning

confidence: 99%

The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity

Flint¹,

Raben²,

Ersbøll³

et al. 2001

Int J Obes

319

228

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OBJECTIVE: Peripheral infusions of glucagon-like peptide-1 (GLP-1) in humans have been shown to inhibit gastrointestinal motility and decrease hunger and energy intake. However, these investigations used supraphysiological doses. The objective of this study was to investigate the effects of a GLP-1 infusion in a physiological dose on appetite sensations, energy intake, gastric emptying, energy and substrate metabolism. METHODS: Eighteen obese men participated in the placebo-controlled, randomized, single-blinded, cross-over study with infusion of GLP-1 or saline. Resting metabolic rate (RMR) and substrate oxidations were measured by ventilated hood before and after an energy-®xed breakfast. Gastric emptying was measured using paracetamol as a marker. Visual analogue scales were used to assess appetite sensations, thirst and comfort throughout the experiment and palatability of the test meals. Blood was sampled for analysis of hormones (GLP-1, GLP-2, glucose-dependent insulinotropic polypeptide (GIP), insulin, glucagon), and substrates (glucose, lactate, non-esteri®ed fatty acids (NEFA), triacylglycerol (TAG)). Ad libitum energy intake at lunch was registered. RESULTS: Following the breakfast, GLP-1 infusion suppressed ratings of hunger and prospective food consumption (P`0.05), whereas all other subjective ratings and ad libitum energy intake were unaffected. RMR, carbohydrate oxidation and gastric emptying rate were lower during the GLP-1 infusion compared with the saline infusion (P`0.001, P`0.05, P`0.0001, respectively). All plasma hormone and substrate pro®les, except NEFA, were signi®cantly reduced by GLP-1 (P`0.0001). CONCLUSION: It is concluded that GLP-1 in physiological concentrations powerfully reduces the rate of entry of nutrients into the circulation by a reduction of gastric emptying rate in obese subjects. The effect of GLP-1 on appetite and food intake may be bene®cial in weight reduction.

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The association between gut hormones and diet‐induced metabolic flexibility in metabolically healthy adults

Unlu

Vinales

Hollstein

et al. 2022

Obesity

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Objective: This study investigated whether interindividual variance in diet-induced metabolic flexibility is explained by differences in gut hormone concentrations.Methods: A total of 69 healthy volunteers with normal glucose regulation underwent 24-hour assessments of respiratory quotient (RQ) in a whole-room indirect calorimeter during eucaloric feeding (EBL; 50% carbohydrate, 30% fat) and then, in a crossover design, during 24-hour fasting and three normal-protein (20%) overfeeding diets (200% energy requirements). Metabolic flexibility was defined as the change in 24-hour RQ from EBL during standard (50% carbohydrate), high-fat (60%), and highcarbohydrate (75%) overfeeding diets. Plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) after an overnight fast were measured prior to and after each diet.Results: Compared with EBL, on average, 24-hour RQ decreased by $4% during high-fat overfeeding, whereas it increased by $4% during standard overfeeding and by $9% during high-carbohydrate overfeeding. During high-carbohydrate overfeeding, but not during any other overfeeding diet or fasting, increased GLP-1 concentration was associated with increased RQ (r = 0.44, p < 0.001), higher/lower carbohydrate/lipid oxidation rates (r = 0.34 and r = À0.51, both p < 0.01), respectively, and increased plasma insulin concentration (r = 0.38, p = 0.02).Conclusions: Increased GLP-1 concentration following high-carbohydrate overfeeding associated with a greater shift to carbohydrate oxidation, suggesting that GLP-1 may be implicated in diet-induced metabolic flexibility to carbohydrate overload.

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Differential Effects of Intracerebroventricular Glucagon-Like Peptide-1 on Feeding and Energy Expenditure Regulation

Cited by 55 publications

References 20 publications

The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans

The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans

The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity

The association between gut hormones and diet‐induced metabolic flexibility in metabolically healthy adults

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