A novel
            GIP
            analogue,
            ZP
            4165, enhances glucagon‐like peptide‐1‐induced body weight loss and improves glycaemic control in rodents

Glucagon-like peptide 1 (GLP-1) is a peptide hormone that is released in response to nutrient ingestion. Postprandial GLP-1 release has been reported to be attenuated in obese subjects, but reports on the effect of weight loss on GLP-1 are conflicting. The aim of the present study was to clarify the effect of a weight-loss period and a consecutive weight-maintenance period on nutrient-stimulated GLP-1 release in obese subjects. Nutrient-stimulated (standard breakfast; 1·9MJ) GLP-1 release was investigated in thirty-two obese subjects on three occasions: before weight loss (T1) (BMI 30·0 (sd 2·5) kg/m2); after a 6-week very-low-energy diet (VLED) (T2) (BMI 27·6 (sd 2·3) kg/m2); after a 3-month weight-maintenance period (T3) (BMI 27·9 (sd 2·3) kg/m2). At each occasion, following a fasting blood sample the test meal was fed and blood was drawn every 30min for 2h relative to ingestion in order to determine plasma GLP-1, insulin, glucose and NEFA concentrations. Subjects lost 7 (sd 3·4) kg during the VLED (P<0·0001) and regained 1 (sd 3·2) kg during the weight-maintenance period (NS). The area under the curve for nutrient-stimulated plasma GLP-1 (pmol/l×h) was significantly decreased (P=0·01) at T2 (6·8 (sd 1)) compared with T1 (12·8 (sd 2·9)) and T3 (11·1 (sd 1·5)). Since we found a rebound of concentrations after a weight-maintenance period, decrease after weight loss seems to be transient and possibly due to a negative energy balance.

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Changes in the Homeostatic Appetite System After Weight Loss Reflect a Normalization Toward a Lower Body Weight

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa202 ◽

2020 ◽

Vol 105 (7) ◽

pp. e2538-e2546 ◽

Cited By ~ 3

Author(s):

Julia Nicole DeBenedictis ◽

Siren Nymo ◽

Karoline Haagensli Ollestad ◽

Guro Akersveen Boyesen ◽

Jens Frederik Rehfeld ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Peptide Yy ◽

Negative Impact ◽

Control Group ◽

Lower Body ◽

Lower Body Weight ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Peptide Secretion

Abstract Objective To compare appetite markers in reduced-obese individuals with a nonobese control group. Methods A total of 34 adults with obesity who lost 17% body weight at week 13 and maintained this weight loss (WL) at 1 year were compared with 33 nonobese controls matched for body composition. Basal and postprandial subjective appetite ratings and appetite-related hormone concentrations (ghrelin, total peptide YY, peptide YY3-36, total and active glucagon-like peptide 1, and cholecystokinin) were measured in all participants and repeated at week 13 and 1 year in the weight-reduced group. Results WL led to a reduction in prospective food consumption and an increase in feelings of hunger, fullness, and ghrelin secretion (basal and postprandial), but these new ratings were no different from those seen in controls. Postprandial concentrations of active glucagon-like peptide 1, total peptide YY, and cholecystokinin were lower in individuals with obesity at all time points compared with controls. Conclusion The increased drive to eat (both subjective feelings of hunger and ghrelin concentrations) seen in reduced-obese individuals, both after acute and sustained WL, reflects a normalization toward a lower body weight. Overall, WL does not have a sustained negative impact on satiety peptide secretion, despite a blunted secretion in individuals with obesity compared with nonobese controls.

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