Conceição E P S, Carvalho J C, Manhães A C, Guarda D S, Figueiredo M S, Quitete F T, Oliveira E, Moura E G, Lisboa P C
Laboratory of Endocrine Physiology, Department of Physiological Sciences, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
J Neuroendocrinol. 2016 May;28(5). doi: 10.1111/jne.12380.
Rats raised in small litters (SL) are obese and hyperphagic. In the present study, we evaluated whether obesity is associated with changes in the mesocorticolimbic dopaminergic reward system in these animals at adulthood. We also assessed the anti-obesity effects of dietary calcium supplementation. To induce early overfeeding, litters were adjusted to three pups on postnatal day (PN)3 (SL group). Control litters were kept with 10 pups each until weaning (NL group). On PN120, SL animals were subdivided into two groups: SL (standard diet) and SL-Ca [SL with calcium supplementation (10 g calcium carbonate/kg rat chow) for 60 days]. On PN175, animals were subjected to a food challenge: animals could choose between a high-fat (HFD) or a high-sugar diet (HSD). Food intake was recorded after 30 min and 12 h. Euthanasia occurred on PN180. SL rats had higher food intake, body mass and central adiposity. Sixty days of dietary calcium supplementation (SL-Ca) prevented these changes. Only SL animals preferred the HFD at 12 h. Both SL groups had lower tyrosine hydroxylase content in the ventral tegmental area, lower dopaminergic transporter content in the nucleus accumbens, and higher type 2 dopamine receptor (D2R) content in the hypothalamic arcuate nucleus (ARC). They also had higher neuropeptide Y (NPY) and lower pro-opiomelanocortin contents in the ARC. Calcium treatment normalised only D2R and NPY contents. Precocious obesity induces long-term effects in the brain dopaminergic system, which can be associated with an increased preference for fat at adulthood. Calcium treatment prevents this last alteration, partially through its actions on ARC D2R and NPY proteins.
在小窝中饲养的大鼠（SL）会出现肥胖和食欲亢进。在本研究中，我们评估了成年期这些动物的肥胖是否与中脑边缘多巴胺能奖赏系统的变化有关。我们还评估了膳食补充钙的抗肥胖作用。为诱导早期过度喂养，在出生后第3天（PN3）将窝仔调整为3只幼崽（SL组）。对照窝仔每窝保留10只幼崽直至断奶（NL组）。在PN120时，将SL动物分为两组：SL（标准饮食）和SL-Ca [补充钙（10 g碳酸钙/千克大鼠饲料）60天的SL组]。在PN175时，对动物进行食物挑战：动物可以在高脂饮食（HFD）或高糖饮食（HSD）之间进行选择。在30分钟和12小时后记录食物摄入量。在PN180时实施安乐死。SL大鼠的食物摄入量、体重和中心性肥胖程度更高。60天的膳食钙补充（SL-Ca）可预防这些变化。仅SL动物在12小时时更喜欢HFD。两个SL组腹侧被盖区的酪氨酸羟化酶含量较低，伏隔核中的多巴胺能转运体含量较低，而下丘脑弓状核（ARC）中的2型多巴胺受体（D2R）含量较高。它们在ARC中的神经肽Y（NPY）含量也较高，而促肾上腺皮质激素原含量较低。钙处理仅使D2R和NPY含量恢复正常。早熟肥胖会在大脑多巴胺能系统中产生长期影响，这可能与成年期对脂肪的偏好增加有关。钙处理可部分通过其对ARC D2R和NPY蛋白的作用来预防这一最后的改变。
