Role of altered renal lipid metabolism in the development of renal injury induced by a high-fat diet
Role of altered renal lipid metabolism in the development of renal injury induced by a high-fat diet
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DOI：
10.1681/asn.2007010089
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发表时间：
2007-10-01
影响因子：
13.6
通讯作者：
Koya, Daisuke
中科院分区：
文献类型：
--
作者：
Kume, Shinji;Uzu, Takashi;Koya, Daisuke
代谢综合征与慢性肾脏病的风险增加有关，代谢综合征患者的肾损伤可能是肾脂质代谢改变的结果。我们用高脂肪饮食喂养野生型或胰岛素敏感的杂合过氧化物酶体增殖物激活受体γ缺陷（PPARγ（+/-））小鼠16周。在野生型小鼠中，这种饮食诱发了代谢综合征、随后的肾脂质积累和肾损伤（包括肾小球硬化、间质纤维化和蛋白尿）的核心特征。肾脏脂肪生成加速，这是由脂肪生成酶脂肪酸合酶和乙酰辅酶A羧化酶（ACC）的肾脏 mRNA 表达增加以及 ACC 活性增加决定的。此外，通过脂肪分解酶肉毒碱棕榈酰辅酶A转移酶1的mRNA表达降低和AMP激活的蛋白激酶的活性降低来确定肾脂肪分解被抑制。在PPAR-gamma(+/-)小鼠中，肾损伤、全身代谢异常、肾脂质蓄积以及肾脂质代谢的变化均减弱。因此，高脂肪饮食会导致肾脏脂肪生成和脂肪分解之间的平衡改变，随后导致肾脏脂质积聚和肾损伤。我们认为肾脂质代谢可以作为预防代谢综合征患者慢性肾脏病的新治疗靶点。
Metabolic syndrome is associated with increased risk of chronic kidney disease, and the renal injury in patients with metabolic syndrome may be a result of altered renal lipid metabolism. We fed wild-type or insulin-sensitive heterozygous peroxisome proliferator-activated receptor gamma-deficient (PPAR gamma(+/-)) mice a high-fat diet for 16 weeks. In wild-type mice, this diet induced core features of metabolic syndrome, subsequent renal lipid accumulation, and renal injury including glomerulosclerosis, interstitial fibrosis, and albuminuria. Renal lipogenesis accelerated, determined by increased renal mRNA expression of the lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase (ACC) and by increased ACC activity. In addition, renal lipolysis was suppressed, determined by reduced mRNA expression of the lipolytic enzyme carnitine palmitoyl acyl-CoA transferase 1 and by reduced activity of AMP-activated protein kinase. In PPAR-gamma(+/-) mice, renal injury, systemic metabolic abnormalities, renal accumulation of lipids, and the changes in renal lipid metabolism were attenuated. Thus, a high-fat diet leads to an altered balance between renal lipogenesis and lipolysis, subsequent renal accumulation of lipid, and renal injury. We suggest that renal lipid metabolism could serve as a new therapeutic target to prevent chronic kidney disease in patients with metabolic syndrome.