Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Front Endocrinol (Lausanne). 2022 Jun 10;13:883092. doi: 10.3389/fendo.2022.883092. eCollection 2022.
The association of high serum prolactin and increased body weight is positive but controversial, therefore we hypothesized that additional factors such as diets and the impact of prolactin on brown adipose tissue may condition its metabolic effects.
We used LacDrd2KO females with lifelong severe hyperprolactinemia due dopamine-D2 receptor deletion from lactotropes, and slow onset of metabolic disturbances, and compared them to their respective controls ). Food intake, and binge eating was evaluated. We then challenged mice with a High Fat (HFD) or a Control Diet (CD) for 8 weeks, beginning at 3 months of age, when no differences in body weight are found between genotypes. At the end of the protocol brown and white adipose tissues were weighed, and thermogenic and lipogenic markers studied, using real time PCR () or immunohistochemistry (UCP1). Histochemical analysis of brown adipose tissue, and glucose tolerance tests were performed.
Hyperprolactinemic mice had increased food intake and binge eating behavior. Metabolic effects induced by a HFD were exacerbated in lacDrd2KO mice. Hyperprolactinemia aggravated HFD-induced body weight gain and glucose intolerance. In brown adipose tissue pronounced cellular as well as decreased expression of the thermogenic markers and were observed in response to high prolactin levels, regardless of the diet, and furthermore, hyperprolactinemia potentiated the decrease in mRNA expression induced by HFD. In subcutaneous white adipose tissue hyperprolactinemia synergistically increased tissue weight, while decreasing , Adiponectin and mRNA levels regardless of the diet.
Pathological hyperprolactinemia has a strong impact in brown adipose tissue, lowering thermogenic markers and evoking tissue whitening. Furthermore, it modifies lipogenic markers in subcutaneous white adipose, and aggravates HFD-induced glucose intolerance and decrease. Therefore, severe high prolactin levels may target BAT function, and furthermore represent an adjuvant player in the development of obesity induced by high fat diets.
高血清催乳素与体重增加呈正相关，但存在争议，因此我们假设其他因素，如饮食和催乳素对棕色脂肪组织的影响，可能会影响其代谢作用。
我们使用由于催乳素细胞中多巴胺-D2 受体缺失而导致终身严重高催乳素血症的 LacDrd2KO 雌性小鼠，以及代谢紊乱发生较晚的小鼠，并将其与各自的对照组进行比较。评估了食物摄入和暴食行为。然后，我们在 3 个月大时开始用高脂肪（HFD）或对照饮食（CD）对小鼠进行 8 周的挑战，此时两种基因型之间的体重没有差异。在方案结束时，称重棕色和白色脂肪组织，并使用实时 PCR（）或免疫组织化学（UCP1）研究生热和脂肪生成标记物。进行了棕色脂肪组织的组织化学分析和葡萄糖耐量试验。
高催乳素血症小鼠的食物摄入量增加，暴食行为增加。HFD 诱导的代谢效应在 lacDrd2KO 小鼠中加剧。高催乳素血症加剧了 HFD 诱导的体重增加和葡萄糖不耐受。在棕色脂肪组织中，无论饮食如何，高催乳素水平都会导致细胞明显增加和产热标记物 和 的表达减少，并且高催乳素血症增强了 HFD 诱导的 表达降低。在皮下白色脂肪组织中，高催乳素血症协同增加组织重量，同时降低 、脂联素和 无论饮食如何，mRNA 水平均降低。
病理性高催乳素血症对棕色脂肪组织有很大影响，降低了产热标记物并引发组织白化。此外，它还改变了皮下白色脂肪中的脂肪生成标记物，并加重了 HFD 诱导的葡萄糖不耐受和 降低。因此，严重的高催乳素水平可能会靶向 BAT 功能，并且是高脂肪饮食诱导肥胖发展的辅助因素。
