The ontogeny of the renal response to continuous systemic infusion of atrial natriuretic peptide (ANP) was studied in chronically instrumented fetal, newborn, and adult nonpregnant sheep. Plasma immunoreactive ANP (ANPir) concentrations during low (0.025 microgram.kg-1.min-1) and high rate (0.1 microgram.kg-1.min-1) ANP infusion were similar between each group of animals. Decrease in renal blood flow velocity (RBFV) and rise in renal vascular resistance (RVR) were observed in fetal and newborn lambs during ANP infusion. The percent changes in RBFV and RVR were of significantly (P less than 0.05) greater magnitude during high ANP infusion rate in fetuses (-28.5 +/- 8.5 and 93 +/- 6.4%) than in adult sheep (-6.6 +/- 3.2 and -4.4 +/- 4.9%). ANP produced no changes in urine flow (V) in fetuses but increased V significantly in newborn lambs and adult sheep. Glomerular filtration rate increased significantly during ANP infusion in adult sheep but not in fetal and newborn lambs. Percentage changes in urinary excretion rate of Na (UNaV) during high ANP infusion rate were significantly higher in adult sheep (3,520 +/- 2,414%) than in newborn (157 +/- 106%) and fetal lambs (198 +/- 84%). These results suggest that the cardiovascular, renal hemodynamic, and possibly renal function responses to continuous ANP infusion increase during maturation, the overall response being larger in adult animals.
Weight regain after weight loss remains a major challenge in obesity treatment and may involve alteration of eating and sedentary behavior after weight loss. In this randomized, controlled, double-blind trial, adults with obesity were randomized, in a 1:1:1:1 ratio stratified by sex and age group (<40 years and ≥40 years), to one-year weight loss maintenance with exercise, the GLP-1 receptor agonist liraglutide, or the combination, as compared with placebo, after low-calorie diet-induced weight loss. Primary outcome was change in body weight, which has been published. Here, we investigated the effects of weight loss maintenance with exercise, liraglutide, or the combination on weight loss-induced changes in the pre-specified explorative outcomes, eating and sedentary behavior in 130 participants who completed the trial according to the study protocol (exercise (n = 26), liraglutide (n = 36), combination (n = 29), and placebo (n = 39)). One year after weight loss, the placebo group had decreased postprandial appetite suppression score by 14%, and increased sedentary time by 31 min/day and regained weight. Liraglutide prevented the decrease in postprandial appetite suppression score compared with placebo (0% vs. −14%; P = 0.023) and maintained weight loss. Exercise after weight loss did not increase appetite or sedentary behavior compared with placebo, despite increased exercise energy expenditure and maintained weight loss. The combination of exercise and liraglutide increased cognitive restraint score (13% vs. −9%; P = 0.042), reflecting a conscious restriction of food intake, and decreased sedentary time by 41 min/day (−10 vs. 31 min/day; 95%CI, −82.3 to −0.2; P = 0.049) compared with placebo, which may have facilitated the additional weight loss. Targeting both eating and sedentary behavior could be the most effective for preventing weight regain.Trial registration: EudraCT number, 2015-005585-32; clinicaltrials.gov number, NCT04122716.
Background: Cardiovascular disease (CVD) is the leading cause of death worldwide and risk factors include obesity, physical inactivity, hypertension, and dyslipidemia. Our aim was to investigate changes in CVD risk factors after an initial weight loss followed by 1 year of treatment with glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide and/or exercise. Method: The trial included 215 individuals with obesity (BMI 36.6 kg/m2, age 42 years). This was a double-blinded trial with an initial 8-week weight loss phase (800 kcal/day) and subsequent randomization (n=195) to placebo, placebo + exercise (150 min/week), liraglutide 3.0 mg/day or liraglutide 3.0 mg/day + exercise (150 min/week) for 1 year. Trial identifier: NCT 04122716 Results: The table shows changes in CVD risk factors after an 8-week weight loss phase followed by 1 year of treatment. Conclusion: A 13 kg weight loss acutely improved all CVD risk factors. With liraglutide and exercise treatment combined, body weight was further reduced. Fasting glucose and HbA1c were additionally improved with the combined treatments compared to placebo and exercise alone. Interestingly, when exercise was added to liraglutide treatment there was no increase in resting heart rate as opposed to liraglutide treatment alone. Disclosure J.R. Lundgren: None. E. Bladbjerg: None. C. Janus: Research Support; Spouse/Partner; Mercodia, Novo Nordisk A/S. Research Support; Self; Novo Nordisk Foundation. Research Support; Spouse/Partner; Novo Nordisk Foundation. Speaker’s Bureau; Spouse/Partner; Merck Sharp & Dohme Corp. L. Gliemann: None. L.M. Olsen: None. C.R. Juhl: None. S.B.K. Jensen: None. R. Thirumathyam: Research Support; Self; Boehringer Ingelheim International GmbH. R.M. Christensen: None. A. Andresen: None. B. Stallknecht: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. J.D. Hove: None. S. Madsbad: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. C. Antoniades: Board Member; Self; Caristo Diagnostics. S.S. Torekov: Research Support; Self; Novo Nordisk Inc. Funding Novo Nordisk Foundation (NNF16OC0019968, NNF15SA0018486); University of Copenhagen; Helsefonden; Danish Diabetes Academy
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