Hashimoto Naoto, Nagata Ryuji, Han Kyu-Ho, Wakagi Manabu, Ishikawa-Takano Yuko, Fukushima Michihiro
Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11, Inada, Obihiro, Hokkaido, 080-8555, Japan.
Division of Food Function Research, Food Research Institute, National Agriculture and Food Research Organization, 2-1-12, Kannondai, Tsukuba, Ibaraki, 305-8642, Japan.
J Physiol Biochem. 2024 Feb;80(1):99-112. doi: 10.1007/s13105-023-00987-9. Epub 2023 Oct 14.
Several humoral factors, such as adiponectin and urate, have been suggested to affect metabolic syndromes. Previously, we reported a reduction in blood adiponectin concentrations after a high-fructose diet partially via the vagus nerve in rats. Although a lithogenic diet (LD), i.e., supplementation of a normal control diet (CT) with 0.6% cholesterol and 0.2% sodium cholate, reduced blood adiponectin concentrations, the involvement of the vagus nerve in this mechanism remains unclear. To estimate the involvement of the vagus nerve in the regulation of blood adiponectin concentrations using an LD, male imprinting control region mice that had been vagotomized (HVx) or only laparotomized (Sham) were administered a CT or an LD for 10 weeks. Serum adiponectin concentrations in the Sham-LD, HVx-CT, and HVx-LD groups were reduced by half compared with the Sham-CT group. The hepatic mRNA levels of fibroblast growth factor 21 (Fgf21), which reportedly stimulates adiponectin secretion from white adipose tissue, were lower in the LD groups compared with the CT groups. HepG2 hepatoma cells showed that various bile acids reduced the mRNA expression of FGF21. Moreover, the LD increased serum urate concentrations and reduced hepatic expressions of the acyl-CoA oxidase 1 (Acox1) mRNA and glucokinase, suggesting insufficient regeneration of ATP from AMP. In conclusion, serum adiponectin concentration may be regulated via the vagus nerve in normal mice, whereas a reduction of hepatic Fgf21 mRNA by bile acids may also lower serum adiponectin levels. Moreover, the LD may promote hepatic AMP accumulation and subsequently increase the serum urate concentration in mice.
已有研究表明，脂联素和尿酸等多种体液因子会影响代谢综合征。此前，我们报道了大鼠在高果糖饮食后，血液中脂联素浓度会部分通过迷走神经降低。虽然致石饮食（LD），即正常对照饮食（CT）中添加0.6%胆固醇和0.2%胆酸钠，会降低血液中脂联素浓度，但迷走神经在这一机制中的作用仍不清楚。为了评估迷走神经在使用LD调节血液脂联素浓度中的作用，对已进行迷走神经切断术（HVx）或仅进行剖腹术（假手术）的雄性印记控制区小鼠给予CT或LD 10周。与假手术-CT组相比，假手术-LD组、HVx-CT组和HVx-LD组的血清脂联素浓度降低了一半。据报道，成纤维细胞生长因子21（Fgf21）可刺激白色脂肪组织分泌脂联素，LD组肝脏中Fgf21的mRNA水平低于CT组。HepG2肝癌细胞显示，多种胆汁酸会降低FGF21的mRNA表达。此外，LD会增加血清尿酸浓度，并降低酰基辅酶A氧化酶1（Acox1）mRNA和葡萄糖激酶的肝脏表达，提示从AMP再生ATP不足。总之，正常小鼠的血清脂联素浓度可能通过迷走神经调节，而胆汁酸降低肝脏Fgf21 mRNA水平也可能降低血清脂联素水平。此外，LD可能促进小鼠肝脏中AMP的积累，进而增加血清尿酸浓度。
