Dietary fructose improves intestinal cell survival and nutrient absorption.
Dietary fructose improves intestinal cell survival and nutrient absorption.
复制标题
膳食果糖改善肠道细胞存活和营养吸收。
DOI：
10.1038/s41586-021-03827-2
复制
发表时间：
2021-09
期刊：
影响因子：
64.8
通讯作者：
Goncalves MD
中科院分区：
文献类型：
--
作者：
Taylor SR;Ramsamooj S;Liang RJ;Katti A;Pozovskiy R;Vasan N;Hwang SK;Nahiyaan N;Francoeur NJ;Schatoff EM;Johnson JL;Shah MA;Dannenberg AJ;Sebra RP;Dow LE;Cantley LC;Rhee KY;Goncalves MD
果糖消费与肥胖和癌症发病率的上升有关，这是全球发病率和死亡率的两个主要原因。膳食果糖代谢开始于小肠上皮，在那里它由GLUT 5运输并由己酮糖激酶磷酸化以形成果糖1-磷酸，其在细胞中积累到高水平。虽然这种途径与肥胖和肿瘤促进有关，但在肠道中驱动这些病理的确切机制仍不清楚。在这里，我们表明，饮食果糖促进肠细胞存活，并增加肠绒毛长度在多个小鼠模型。增加绒毛长度扩大肠道表面积，增加营养吸收和高脂肪饮食喂养的小鼠肥胖。在缺氧的肠细胞中，1-磷酸果糖抑制丙酮酸激酶的M2亚型以促进细胞存活。基因切除己酮糖激酶或刺激丙酮酸激酶可防止绒毛伸长，并消除HFCs促进的营养吸收和肿瘤生长。因此，果糖通过变构代谢物促进细胞存活的能力为西方饮食相关的肥胖提供了额外的见解，并为HFCs促进肿瘤生长提供了令人信服的解释。
Fructose consumption is linked to the rising incidence of obesity and cancer, two of the leading causes of morbidity and mortality globally. Dietary fructose metabolism begins at the small intestine epithelium, where it is transported by GLUT5 and phosphorylated by ketohexokinase to form fructose 1-phosphate, which accumulates to high levels in the cell. While this pathway is implicated in obesity and tumor promotion, the exact mechanism driving these pathologies in the intestine remains unclear. Here, we show that dietary fructose promotes intestinal cell survival and increases intestinal villus length across multiple murine models. Increased villus length expands gut surface area and increases nutrient absorption and adiposity in mice fed a high-fat diet. In hypoxic intestinal cells, fructose 1-phosphate inhibits the M2 isoform of pyruvate kinase to promote cell survival. Genetic ablation of ketohexokinase or stimulation of pyruvate kinase prevents villus elongation and abolishes HFCS-promoted nutrient absorption and tumor growth. The ability of fructose to promote cell survival via an allosteric metabolite thus provides additional insight into Western-diet associated adiposity and a compelling explanation for HFCS-promoted tumor growth.