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Loss-of-function G6PD variant moderated high-fat diet-induced obesity, adipocyte hypertrophy, and fatty liver in male rats.
Matsumura, Shun; Signoretti, Christina; Fatehi, Samuel; Tumenbayar, Bat Ider; D'Addario, Catherine; Nimmer, Erik; Thomas, Colin; Viswanathan, Trisha; Wolf, Alexandra; Garcia, Victor; Rocic, Petra; Bae, Yongho; Alam, Sm Shafiqul; Gupte, Sachin A.
Afiliación
  • Matsumura S; Department of Pharmacology, New York Medical College, Valhalla, New York, USA.
  • Signoretti C; Department of Pharmacology, New York Medical College, Valhalla, New York, USA.
  • Fatehi S; Department of Pharmacology, New York Medical College, Valhalla, New York, USA.
  • Tumenbayar BI; Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
  • D'Addario C; Department of Pharmacology, New York Medical College, Valhalla, New York, USA.
  • Nimmer E; Department of Biomedical Engineering, School of Engineering and Applied Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
  • Thomas C; Department of Biomedical Engineering, School of Engineering and Applied Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
  • Viswanathan T; Department of Pharmacology, New York Medical College, Valhalla, New York, USA.
  • Wolf A; Department of Pharmacology, New York Medical College, Valhalla, New York, USA.
  • Garcia V; Department of Pharmacology, New York Medical College, Valhalla, New York, USA.
  • Rocic P; Department of Physiology & Pharmacology, SHSU College of Osteopathic Medicine, Conroe, Texas, USA.
  • Bae Y; Department of Biomedical Engineering, School of Engineering and Applied Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA; Department of Pathology and Anatomical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University o
  • Alam SS; Department of Pathology, Microbiology, and Immunology (PMI), New York Medical College, Valhalla, New York, USA.
  • Gupte SA; Department of Pharmacology, New York Medical College, Valhalla, New York, USA. Electronic address: s_gupte@nymc.edu.
J Biol Chem ; 300(7): 107460, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38876306
ABSTRACT
Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased , glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases. G6PD is induced by a carbohydrate-rich diet and insulin. Long-term (8 months) high-fat diet (HFD) feeding increased body weight and elicited metabolic reprogramming in visceral fat, liver, and aorta, of the wild-type rats. In addition, HFD increased inflammatory chemokines in visceral fat. Interestingly, CRISPR-edited loss-of-function Mediterranean G6PD variant (G6PDS188F) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PDS188F variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PDS188F variant increased Magel2 - a gene encoding circadian clock-related protein that suppresses obesity associated with Prader-Willi syndrome - and reduced HFD-induced non-alcoholic fatty liver. Additionally, the G6PDS188F variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adipocitos / Hígado Graso / Dieta Alta en Grasa / Glucosafosfato Deshidrogenasa / Hipertrofia / Obesidad Límite: Animals Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adipocitos / Hígado Graso / Dieta Alta en Grasa / Glucosafosfato Deshidrogenasa / Hipertrofia / Obesidad Límite: Animals Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos