16/8 intermittent fasting in mice protects from diet-induced obesity by increasing leptin sensitivity and postprandial thermogenesis

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Arruda, Adriano Cleis ; Santos, Raisa Brito ; Freitas-Lima, Leandro Ceotto ; Budu, Alexandre ; Perilhao, Mauro Sergio ; Wasinski, Frederick ; Arthur, Gabriel Melo ; Guzman, Roger Rodrigues ; Gomes, Guilherme ; Pesquero, Joao Bosco ; Mecawi, Andre Souza ; Bader, Michael ; Keller, Alexandre Castro ; Donato Junior, Jose ; Festuccia, Willian Tadeu ; Mori, Marcelo A. ; Araujo, Ronaldo Carvalho

• Document type: Journal article
• Source: ACTA PHYSIOLOGICA; v. 241, n. 5, p. 13-pg., 2025-05-01.

Abstract

Aims: To evaluate the molecular mechanisms involved in intermittent fasting 16/8 (16/8 IF), a widespread dietary practice adopted worldwide that consists of 16 h of fasting and 8 h of feeding. Methods: Obese mice were fasted daily from 6 am to 10 pm. Food intake, body weight, and energy expenditure were measured. Molecular mechanisms were investigated using ELISA, western blot, and qPCR of white and brown adipose tissues. Glucose homeostasis was also evaluated. Ucp1 knockout and ob/ob mice were utilized. Results: The 16/8 IF regimen improved glucose homeostasis and reduced body weight, food intake, and overall adiposity. Postprandial VO2, heat production, brown adipose tissue (BAT) temperature, and ketone bodies increased with 16/8 IF. Postprandial thermogenesis induced by 16/8 IF was abolished in mice after BAT denervation or Ucp1 deletion. Serum leptin levels were elevated, and most metabolic effects of 16/8 IF were absent in leptin-deficient ob/ob mice. Additionally, leptin sensitivity increased in mice exposed to 16/8 IF. Conclusion: The 16/8 IF regimen can improve metabolism, with findings underscoring the role of enhanced leptin action in inhibiting food intake and promoting postprandial thermogenesis during 16/8 IF. (AU)

• FAPESP's process: 21/14313-7 - Role of kallikrein kinin system on metabolism and repercussion on voluntary exercise
• Grantee: Ronaldo de Carvalho Araújo
• Support Opportunities: Research Projects - Thematic Grants