Soto Marion, Chaumontet Catherine, Mauduit Charles-David, Fromentin Gilles, Palme Rupert, Tomé Daniel, Even Patrick
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.
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.
Physiol Behav. 2016 Feb 1;154:175-83. doi: 10.1016/j.physbeh.2015.11.012. Epub 2015 Nov 17.
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.
饮用含糖饮料与超重和肥胖有关。在本研究中，我们假设高脂高糖饮食（HFHS）喂养的易肥胖（OP）小鼠比抗肥胖（OR）小鼠对蔗糖水（SSW）的摄入更敏感。在随意进食HFHS饮食3周（每天7.5小时）后，180只雄性小鼠被分为OP组（体重增加上四分位数，5.2±0.1克，n = 45）或OR组（体重增加下四分位数，3.2±0.1克，n = 45）。随后，OP和OR小鼠被分为3个亚组，这些亚组可随意进食HFHS饮食（每天7.5小时）16周，并补充：i）水（OP/水和OR/水）；ii）水和SSW（12.6% w/v），在可随意进食HFHS饮食时每天随机供应2小时，每周随机选择5天供应（OP/SSW和OR/SSW）；或iii）水和SSW供应8周，然后仅供应水8周（OP/SSW-水和OR/SSW-水）。与OR/水小鼠相比，OR/SSW小鼠的食物摄入量减少，而与OP/水小鼠相比，OP/SSW小鼠的食物摄入量和总能量摄入量增加。OP/SSW小鼠的体重和脂肪量也比OP/水小鼠增加更多，肝脏甘油三酯增加，并出现胰岛素抵抗。这些影响在OP/SSW-水小鼠中完全逆转。在肠道中，与仅饮水的小鼠相比，OR/SSW小鼠对液体餐的GLP-1和CCK反应增加，但OP/SSW小鼠没有。与禁食时的OP/水小鼠相比，OP/SSW小鼠下丘脑黑皮质素受体4的表达降低，伏隔核中δ阿片受体的表达增加，这可以解释这些小鼠的摄食亢进。当蔗糖溶液供应中断8周时，OP小鼠对蔗糖溶液的多巴胺能和阿片样物质反应增强。因此，在喂食HFHS饮食的小鼠中间歇性供应蔗糖溶液会引起肠道和大脑信号的变化，仅在易患HFHS诱导肥胖的小鼠中导致能量摄入增加和不良代谢后果。
