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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Arcuate Nucleus Overexpression of NHLH2 Reduces Body Mass and Attenuates Obesity-Associated Anxiety/ Depression-like Behavior

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Carraro, Rodrigo S. [1] ; Nogueira, Guilherme A. [1] ; Sidarta-Oliveira, Davi [1] ; Gaspar, Rodrigo S. [1] ; Dragano, Nathalia R. [1] ; Morari, Joseane [1] ; Bobbo, Vanessa C. D. [1] ; Araujo, Eliana P. [1] ; Mendes, Natalia F. [1] ; Zanesco, Ariane M. [1] ; Tobar, Natalia [2] ; Ramos, Celso D. [2] ; Toscaro, Jessica M. [3] ; Bajgelman, Marcio C. [3] ; Velloso, Licio A. [1, 4]
Total Authors: 15
[1] Univ Estadual Campinas, Obes & Comorbid Res Ctr, Lab Cell Signaling, BR-13083970 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Nucl Med Serv, Dept Radiol, Hosp Clin, BR-13083970 Campinas, SP - Brazil
[3] Brazilian Ctr Res Energy & Mat, Brazilian Biosci Natl Lab, BR-13083970 Campinas, SP - Brazil
[4] Natl Inst Sci & Technol, Neuroimmunomodulat, BR-21040900 Fiocruz, RJ - Brazil
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF NEUROSCIENCE; v. 41, n. 48, p. 10004-10022, DEC 1 2021.
Web of Science Citations: 1

Nescient helix-loop-helix 2 (NHLH2) is a hypothalamic transcription factor that controls the expression of prohormone convertase 1/ 3, therefore having an impact on the processing of proopiomelanocortin and thus on energy homeostasis. Studies have shown that KO of Nhlh2 results in increased body mass, reduced physical activity, and hypogonadism. In humans, a polymorphism of the NHLH2 gene is associated with obesity; and in Prader-Willi syndrome, a condition characterized by obesity, hypogonadism and behavioral abnormalities, the expression of NHLH2 is reduced. Despite clinical and experimental evidence suggesting that NHLH2 could be a good target for the treatment of obesity, no previous study has evaluated the impact of NHLH2 overexpression in obesity. Here, in mice fed a high-fat diet introduced right after the arcuate nucleus intracerebroventricular injection of a lentivirus that promoted 40% increase in NHLH2, there was prevention of the development of obesity by a mechanism dependent on the reduction of caloric intake. When hypothalamic overexpression of NHLH2 was induced in previously obese mice, the beneficial impact on obesity-associated phenotype was even greater; thus, there was an 80% attenuation in body mass gain, reduced whole-body adiposity, increased brown adipose tissue temperature, reduced hypothalamic inflammation, and reduced liver steatosis. In this setting, the beneficial impact of hypothalamic overexpression of NHLH2 was a result of combined effects on caloric intake, energy expenditure, and physical activity. Moreover, the hypothalamic overexpression of NHLH2 reduced obesity-associated anxiety/depression behavior. Thus, we provide an experimental proof of concept supporting that hypothalamic NHLH2 is a good target for the treatment of obesity. (AU)

FAPESP's process: 16/00977-2 - Evaluation of expression and distribution of Nhlh2 protein in the hypothalamus of animals subjected to high fat diet
Grantee:Rodrigo Scarpari Carraro
Support type: Scholarships in Brazil - Doctorate