Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM).
Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec, Canada.
Obesity (Silver Spring). 2016 Sep;24(9):1946-54. doi: 10.1002/oby.21592. Epub 2016 Jul 26.
Administration of the handle region peptide (HRP), a (pro)renin receptor blocker, decreases body weight gain and visceral adipose tissue (VAT) in high-fat/high-carbohydrate (HF/HC) diet-fed mice. The objective of this study was to elucidate potential mechanisms implicated in these observations.
Mice were given a normal or a HF/HC diet along with saline or HRP for 10 weeks.
In HF/HC-fed mice, HRP increased the expression of several enzymes implicated in lipogenesis and lipolysis in subcutaneous fat (SCF) while the expression of the enzyme implicated in the last step of lipogenesis decreased in VAT. A reduction was also observed in circulating free fatty acids in these animals which was accompanied by normalized adipocyte size in VAT and increased adipocyte size in SCF. ''Beiging'' is the evolution of a white adipose tissue toward a brown-like phenotype characterized by an increased mitochondrial density and small lipid droplets. HRP increased the expression of' "beiging" markers in SCF of HF/HC diet-fed mice.
HRP treatment may favor healthy fat storage in SCF by activating a triglyceride/free fatty acid cycling and "beiging," which could explain the body weight and fat mass reduction.
手柄区肽（HRP）是一种（前）肾素受体阻滞剂，可降低高脂肪/高碳水化合物（HF/HC）饮食喂养的小鼠的体重增加和内脏脂肪组织（VAT）。本研究的目的是阐明这些观察结果所涉及的潜在机制。
将小鼠给予正常饮食或 HF/HC 饮食，并给予生理盐水或 HRP 喂养 10 周。
在 HF/HC 喂养的小鼠中，HRP 增加了皮下脂肪（SCF）中几种参与脂肪生成和脂肪分解的酶的表达，而参与脂肪生成最后一步的酶的表达在 VAT 中降低。在这些动物中还观察到循环游离脂肪酸减少，同时 VAT 中的脂肪细胞大小正常化，SCF 中的脂肪细胞大小增加。“褐变”是白色脂肪组织向类似于棕色的表型的演变，其特征为线粒体密度增加和小脂质滴。HRP 增加了 HF/HC 饮食喂养小鼠 SCF 中“褐变”标志物的表达。
HRP 治疗可能通过激活甘油三酯/游离脂肪酸循环和“褐变”来促进 SCF 中健康的脂肪储存，这可以解释体重和脂肪质量的减少。
