title: Excessive eccentric exercise leads to transitory hypothalamic inflammation, which may contribute to the low body weight gain and food intake in overtrained mice.
abstract: Low body weight gain and food intake are related to exhaustive training and overtraining; however, the molecular mechanisms responsible for these alterations remain unknown. The main aim of this study was to evaluate the effects of running overtraining (OT) protocols performed downhill, uphill and without inclination on the inflammatory pathway in the mouse hypothalamus. The rodents were randomized into the control (C), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR) groups. The body weights and food intake were recorded daily. The incremental load, exhaustive, rotarod and grip force tests were used to measure performance. At 36 h after the grip force test was performed at the end of OT protocols (i.e., week eight) and/or after a 2-week total recovery period (i.e., week 10), the hypothalamus and gastrocnemius were extracted for immunoblotting analysis. In addition, the serum was used to determine cytokine and leptin concentrations. From week 0 to week 8, the OTR/down group exhibited decreased body weight and food intake, and the OTR/up group increased their food intake. At week 10, the OTR/down group exhibited increased body weight, while the OTR group decreased their food intake. The OTR/down group exhibited increased IL-1beta, IL-6, TNF-alpha, pSAPK/JNK and SOCS3 levels at week eight. The OTR/down, OTR/up and OTR groups exhibited increased IL-10 levels at week 10. The OTR/up group displayed increased pJAK2 levels at week eight. While the OTR/down group exhibited increased IL-1beta levels, the OTR/down and OTR/up groups exhibited increased IL-6 and TNF-alpha levels, but decreased IL-10 levels in the gastrocnemius at week eight. The three OT protocols increased the IL-1beta and IL-6 levels, but only the OTR/down and OTR/up groups had increased TNF-alpha levels in serum at week eight. The serum leptin levels were lower for the OTR group compared with the CT group at week eight. In conclusion, the OTR/down protocol induced transitory hypothalamic inflammation with concomitant reductions in the body weight and food intake. After the 2-week total recovery period, the OTR/down group had reversed the hypothalamic inflammation, with the concomitant normalization of the body weight and food intake.
authors.affiliation: Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: B C
authors.initials: BC
authors.lastname: Pereira
authors.affiliation: Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: da Rocha
authors.affiliation: Sport Sciences Course, Faculty of Applied Sciences, State University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
authors.forename: J R
authors.initials: JR
authors.lastname: Pauli
authors.affiliation: Sport Sciences Course, Faculty of Applied Sciences, State University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
authors.forename: E R
authors.initials: ER
authors.lastname: Ropelle
authors.affiliation: Exercise Biochemistry and Physiology Laboratory Postgraduate Program in Health Sciences, Health Sciences Unit, University of Far Southern Santa Catarina, Criciúma, Santa Catarina, Brazil.
authors.forename: C T
authors.initials: CT
authors.lastname: de Souza
authors.affiliation: Sport Sciences Course, Faculty of Applied Sciences, State University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
authors.forename: D E
authors.initials: DE
authors.lastname: Cintra
authors.affiliation: Sport Sciences Course, Faculty of Applied Sciences, State University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Sant'Ana
authors.affiliation: Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil. Electronic address: adelinosanchez@usp.br.
authors.forename: A S R
authors.initials: AS
authors.lastname: da Silva
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004435:Eating / Q000502:physiology*; D018737:Hand Strength / Q000502:physiology; D007031:Hypothalamus / Q000276:immunology*; D007249:Inflammation / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D018482:Muscle, Skeletal / Q000276:immunology; D011897:Random Allocation; D045442:Rotarod Performance Test; D012420:Running / Q000502:physiology*; D057185:Sedentary Behavior
chemical_list: D016207:Cytokines; D020738:Leptin
keywords: eccentric exercise; hypothalamus; inflammation; overtraining