Kathy C G de Git1, Céline Peterse1, Sanne Beerens1, Mieneke C M Luijendijk1, Geoffrey van der Plasse1, Susanne E la Fleur2, Roger A H Adan3,4. 1. Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CG, The Netherlands. 2. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands. 3. Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CG, The Netherlands. r.a.h.adan@umcutrecht.nl. 4. Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. r.a.h.adan@umcutrecht.nl.
Abstract
BACKGROUND/ OBJECTIVES: Obesity is strongly associated with leptin resistance. It is unclear whether leptin resistance results from the (over)consumption of energy-dense diets or if reduced leptin sensitivity is also a pre-existing factor in rodent models of diet-induced obesity (DIO). We here tested whether leptin sensitivity on a chow diet predicts subsequent weight gain and leptin sensitivity on a free choice high-fat high-sucrose (fcHFHS) diet. METHODS: Based upon individual leptin sensitivity on chow diet, rats were grouped in leptin sensitive (LS, n = 22) and leptin resistant (LR, n = 19) rats (P = 0.000), and the development of DIO on a fcHFHS diet was compared. The time-course of leptin sensitivity was measured over weeks in individual rats. RESULTS: Both on a chow and a fcHFHS diet, high variability in leptin sensitivity was observed between rats, but not over time per individual rat. Exposure to the fcHFHS diet revealed that LR rats were more prone to develop DIO (P = 0.013), which was independent of caloric intake (p ≥ 0.320) and the development of diet-induced leptin resistance (P = 0.769). Reduced leptin sensitivity in LR compared with LS rats before fcHFHS diet exposure, was associated with reduced leptin-induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3) levels in the dorsomedial and ventromedial hypothalamus (P ≤ 0.049), but not the arcuate nucleus (P = 0.558). CONCLUSIONS: A pre-existing reduction in leptin sensitivity determines the susceptibility to develop excessive DIO after fcHFHS diet exposure. Rats with a pre-existing reduction in leptin sensitivity develop excessive DIO without eating more calories or altering their leptin sensitivity.
BACKGROUND/ OBJECTIVES:Obesity is strongly associated with leptin resistance. It is unclear whether leptin resistance results from the (over)consumption of energy-dense diets or if reduced leptin sensitivity is also a pre-existing factor in rodent models of diet-induced obesity (DIO). We here tested whether leptin sensitivity on a chow diet predicts subsequent weight gain and leptin sensitivity on a free choice high-fat high-sucrose (fcHFHS) diet. METHODS: Based upon individual leptin sensitivity on chow diet, rats were grouped in leptin sensitive (LS, n = 22) and leptin resistant (LR, n = 19) rats (P = 0.000), and the development of DIO on a fcHFHS diet was compared. The time-course of leptin sensitivity was measured over weeks in individual rats. RESULTS: Both on a chow and a fcHFHS diet, high variability in leptin sensitivity was observed between rats, but not over time per individual rat. Exposure to the fcHFHS diet revealed that LR rats were more prone to develop DIO (P = 0.013), which was independent of caloric intake (p ≥ 0.320) and the development of diet-induced leptin resistance (P = 0.769). Reduced leptin sensitivity in LR compared with LS rats before fcHFHS diet exposure, was associated with reduced leptin-induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3) levels in the dorsomedial and ventromedial hypothalamus (P ≤ 0.049), but not the arcuate nucleus (P = 0.558). CONCLUSIONS: A pre-existing reduction in leptin sensitivity determines the susceptibility to develop excessive DIO after fcHFHS diet exposure. Rats with a pre-existing reduction in leptin sensitivity develop excessive DIO without eating more calories or altering their leptin sensitivity.
Authors: Margo Slomp; Evita Belegri; Aurea S Blancas-Velazquez; Charlene Diepenbroek; Leslie Eggels; Myrtille C R Gumbs; Anil Joshi; Laura L Koekkoek; Khalid Lamuadni; Muzeyyen Ugur; Unga A Unmehopa; Susanne E la Fleur; Joram D Mul Journal: J Neuroendocrinol Date: 2019-04-24 Impact factor: 3.627
Authors: Kathy C G de Git; Johannes A den Outer; Inge G Wolterink-Donselaar; Mieneke C M Luijendijk; Erik Schéle; Suzanne L Dickson; Roger A H Adan Journal: Physiol Rep Date: 2019-07
Authors: Vincent Ten Cate; Thomas Koeck; Jürgen Prochaska; Andreas Schulz; Marina Panova-Noeva; Steffen Rapp; Lisa Eggebrecht; Michael Lenz; Julia Glunz; Madeleine Sauer; Raff Ewert; Michael Halank; Thomas Münzel; Stefan Heitmeier; Miguel A Andrade-Navarro; Karl J Lackner; Stavros V Konstantinides; Kirsten Leineweber; Philipp S Wild Journal: Blood Adv Date: 2021-07-27
Authors: Eulla Keimili Fernandes Ferreira Cavalheiro; Ana Beatriz Costa; Daniéle Hendler Salla; Mariella Reinol da Silva; Talita Farias Mendes; Larissa Espindola da Silva; Cristini da Rosa Turatti; Rafael Mariano de Bitencourt; Gislaine Tezza Rezin Journal: Cannabis Cannabinoid Res Date: 2021-07-09