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Horm Metab Res 2025; 57(03): 199-207
DOI: 10.1055/a-2420-6549
Original Article: Endocrine Care

Influence of Mitochondrial NAD(P) +  Transhydrogenase (NNT) on Hypothalamic Inflammation and Metabolic Dysfunction Induced by a High-Fat Diet in Mice

Giovanna Leite Santos
1   Department of Pathology, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Ericka Francislaine Dias Costa
1   Department of Pathology, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Ana Paula Dalla Costa
1   Department of Pathology, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Ariane Maria Zanesco
2   Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Marcela Reymond Simoes
2   Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Fábio Rogério
1   Department of Pathology, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Daniele Masselli Rodrigues Demolin
3   Multidisciplinary Center for Biological Investigation on Laboratory Animals Science, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Claudia Daniele Carvalho Navarro
1   Department of Pathology, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Lício Augusto Velloso
2   Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Annelise Francisco 
4   Department of Experimental Medical Science, Lunds Universitet, Lund, Sweden (Ringgold ID: RIN5193)
1   Department of Pathology, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
,
Roger Frigério Castilho
1   Department of Pathology, State University of Campinas (UNICAMP), Campinas, Brazil (Ringgold ID: RIN28132)
› InstitutsangabenGefördert durch: Conselho Nacional de Desenvolvimento Científico e Tecnológico 305231/2022-7, INCT-SC 406020/2022-1
Gefördert durch: Fundação de Amparo à Pesquisa do Estado de São Paulo 17/17728-8, 23/00229-0, 23/06469-2
Gefördert durch: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES/STINT 88887.724090/2022-00
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Abstract

The mitochondrial protein NAD(P)+ transhydrogenase (NNT) has been implicated in the metabolic derangements observed in obesity. Mice with the C57BL/6J genetic background bear a spontaneous mutation in the Nnt gene and are known to exhibit increased susceptibility to diet-induced metabolic disorders. Most of the studies on NNT in the context of diet-induced obesity have compared C57BL/6J mice with other mouse strains, where differences in genetic background can serve as confounding factors. Moreover, these studies have predominantly employed a high-fat diet (HFD) consisting of approximately 60% of calories from fat, which may not accurately mimic real-world fat-rich diets. In this study, we sought to examine the role of NNT in diet-induced hypothalamic inflammation and metabolic syndrome by using a congenic mice model lacking NNT, along with a HFD providing approximately 45% of calories from fat. Our findings indicate that mice lacking NNT were more protected from HFD-induced weight gain but presented a worse performance on glucose tolerance test, albeit not in insulin tolerance test. Interestingly, the brown adipose tissue of HFD-fed Nnt +/+ mice presented a greater mass and a higher whole-tissue ex-vivo oxygen consumption rate. Also, HFD increased the expression of the inflammatory markers Il1β, Tlr4 and Iba1 in the hypothalamus of Nnt –/– mice. In conclusion, our study highlights the importance of NNT in the context of diet-induced obesity and metabolic syndrome, indicating its contribution to mitigate hypothalamic inflammation and suggesting its role in the brown adipose tissue increased mass.

Keywords

brown adipose tissue - glucose homeostasis - high fat diet - hypothalamic inflammation - NADPH - nicotinamide nucleotide transhydrogenase

Supplementary Material



Publikationsverlauf

Eingereicht: 20. Juni 2024

Angenommen nach Revision: 19. September 2024

Artikel online veröffentlicht:
31. Oktober 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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