title: Intermittent access to a sucrose solution impairs metabolism in obesity-prone but not obesity-resistant mice.
abstract: Consumption of sugar-sweetened beverages is associated with overweight and obesity. In this study, we hypothesized that obesity-prone (OP) mice fed a high-fat high-sucrose diet (HFHS) are more sensitive to consumption of sucrose-sweetened water (SSW) than obesity-resistant (OR) mice. After 3weeks of ad libitum access to the HFHS diet (7.5h/day), 180 male mice were classified as either OP (upper quartile of body weight gain, 5.2±0.1g, n=45) or OR (lower quartile, 3.2±0.1g, n=45). OP and OR mice were subsequently divided into 3 subgroups that had access to HFHS (7.5h/day) for 16weeks, supplemented with: i) water (OP/water and OR/water); ii) water and SSW (12.6% w/v), available for 2h/day randomly when access to HFHS was available and for 5 randomly-chosen days/week (OP/SSW and OR/SSW); or iii) water and SSW for 8weeks, then only water for 8weeks (OP/SSW-water and OR/SSW-water). OR/SSW mice decreased their food intake compared to OR/water mice, while OP/SSW mice exhibited an increase in food and total energy intake compared to OP/water mice. OP/SSW mice also gained more body weight and fat mass than OP/water mice, showed an increase in liver triglycerides and developed insulin resistance. These effects were fully reversed in OP/SSW-water mice. In the gut, OR/SSW mice, but not OP/SSW mice, had an increase GLP-1 and CCK response to a liquid meal compared to mice drinking only water. OP/SSW mice had a decreased expression of melanocortin receptor 4 in the hypothalamus and increased expression of delta opioid receptor in the nucleus accumbens compared to OP/water mice when fasted that could explain the hyperphagia in these mice. When access to the sucrose solution was removed for 8weeks, OP mice had increased dopaminergic and opioidergic response to a sucrose solution. Thus, intermittent access to a sucrose solution in mice fed a HFHS diet induces changes in the gut and brain signaling, leading to increased energy intake and adverse metabolic consequences only in mice prone to HFHS-induced obesity.
authors.affiliation: AgroParisTech, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France; INRA, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France. Electronic address: Marion.Soto@joslin.harvard.edu.
authors.forename: Marion
authors.initials: M
authors.lastname: Soto
authors.affiliation: AgroParisTech, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France; INRA, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chaumontet
authors.affiliation: AgroParisTech, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France; INRA, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France.
authors.forename: Charles-David
authors.initials: CD
authors.lastname: Mauduit
authors.affiliation: AgroParisTech, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France; INRA, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Fromentin
authors.affiliation: Department of Biomedical Sciences/Biochemistry, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Palme
authors.affiliation: AgroParisTech, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France; INRA, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tomé
authors.affiliation: AgroParisTech, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France; INRA, CRNH-IdF, UMR0914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Even
mesh_terms: D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004326:Drinking; D004435:Eating; D004734:Energy Metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D005951:Glucose Tolerance Test; D006963:Hyperphagia / Q000139:chemically induced*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000503:physiopathology*; D013395:Sucrose / Q000009:adverse effects* / Q000378:metabolism; D013549:Sweetening Agents / Q000009:adverse effects* / Q000378:metabolism
chemical_list: D013549:Sweetening Agents; D013395:Sucrose; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin
keywords: Body composition; Brain neuropeptides; Diet-induced obesity; High-fat high-sucrose diet; Scheduled feeding; Sugar-sweetened beverages