PPARa Dependent Regulation of Gut Microbiota: Implication for Host Metabolic Homeostasis
Por:
Sánchez-Tapia, M, Tobón-Cornejo, S, Guevara-Cruz, M, Velázquez-Villegas, LA, Hernández-Pando, R, López-Barradas, A, Guizar-Heredia, R, Maya, O, Furuzawa-Carballeda, J, Rebollar-Vega, R, Vargas-Castillo, A, Torres, N, Tovar, AR
Publicada:
13 jul 2026
Resumen:
The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a key regulator of lipid metabolism and energy homeostasis. However, its role in shaping the gut microbiota requires further investigation. Therefore, the aim of the present study was to investigate whether the lack of PPAR alpha in a mouse model or the presence of a single nucleotide polymorphism (SNP) rs6008259 of PPAR alpha in humans can modulate the gut microbiota and its association with metabolic alterations. PPAR alpha-/- and PPAR+/+ male mice were fed an AIN-93 diet for 10 days, and a human cohort (n = 177) was genotyped for the PPAR alpha SNP rs6008259. PPAR alpha-/- mice showed less body weight gain, more fat mass and reduced lean mass compared to WT, despite similar food intake. They exhibited elevated hepatic triglycerides and hyperlipidemia. In humans, carriers of the rs6008259 allele of PPAR alpha showed similar findings in blood lipids and body composition. Colonic analysis revealed reduced hypoxia in PPAR alpha-/- mice, increased inflammatory markers, and compromised barrier function. Gut microbiota analysis in PPAR alpha-/- mice and humans, carriers of the rs6008259 allele of PPAR alpha showed reduced alpha diversity and altered composition, including increased Blautia, Parabacteroides and Lanchoclostridium. Genetic background is important in the interpretation on the effects of diet on gut microbiota.
Filiaciones:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Fisiol Nutr, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Patol Expt, Mexico City, Mexico
Chalmers Univ Technol, Phys Dept, Gothenburg, Sweden
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cirugia Expt, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Red Apoyo Invest, Coordinac Invest Cient, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, Mexico
Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA
Harvard Med Sch, Dept Cell Biol, Boston, MA USA
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