Hepatic peroxisome proliferator-activated receptor-gamma-fat-specific protein 27 pathway contributes to obesity-related hypertension via afferent vagal signals

作者：Uno Kenji; Yamada Tetsuya; Ishigaki Yasushi; Imai Junta; Hasegawa Yutaka; Gao Junhong; Kaneko Keizo; Matsusue Kimihiko; Yamazaki Tomomi; Oka Yoshitomo; Katagiri Hideki^*

来源：European Heart Journal, 2012, 33(10): 1279-1289.

DOI：10.1093/eurheartj/ehr265

• Obesity
• Hypertension
• Neuronal signals
• PPAR
• Fsp27

Obesity is commonly associated with hypertension. Increased sympathetic tonus in obese subjects contributes to the underlying mechanism. However, the precise mechanisms whereby obesity induces this sympathetic activation remain unclear. Hepatic peroxisome proliferator-activated receptor (PPAR)-2 expression, which is reportedly upregulated during obesity development, affects sympathetic activation via hepatic vagal afferents. Herein, we report involvement of this neuronal relay in obesity-related hypertension. %26lt;br%26gt;Peroxisome proliferator-activated receptor- and a direct PPAR target, fat-specific protein 27 (Fsp27), were adenovirally overexpressed or knocked down in the liver, in combination with surgical dissection or pharmacological deafferentation of the hepatic vagus. Adenoviral PPAR2 expression in the liver raised blood pressure (BP) in wild-type but not in 1/2/3 adrenergic receptor-deficient mice. In addition, knockdown of endogenous PPAR in the liver lowered BP in murine obesity models. Either surgical dissection or pharmacological deafferentation of the hepatic vagus markedly blunted BP elevation in mice with diet-induced and genetically-induced obesity. In contrast, BP was not elevated in other models of hepatic steatosis, DGAT1 and DGAT2 overexpressions, in which PPAR is not upregulated in the liver. Thus, hepatic PPAR upregulation associated with obesity is involved in BP elevation during obesity development. Furthermore, hepatic expression of Fsp27 raised BP and the effect was blocked by hepatic vagotomy. Hepatic Fsp27 is actually upregulated in murine obesity models and its knockdown reversed BP elevation. %26lt;br%26gt;The hepatic PPARFsp27 pathway plays important roles in the development of obesity-related hypertension via afferent vagal signals from the liver.

• 出版日期2012-5