RESUMO
Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction and preservation of GI emptying and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.
Assuntos
Comportamento Animal/efeitos dos fármacos , Curcumina/administração & dosagem , Doença de Huntington/dietoterapia , Redução de Peso/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Curcumina/farmacologia , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Doença de Huntington/fisiopatologia , Masculino , Camundongos , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , FenótipoRESUMO
BACKGROUND: Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults. OBJECTIVE: The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest. DESIGN: We used a randomized, double-blind, placebo-controlled trial to assess changes in skeletal MPS, cellular signaling, body composition, and skeletal muscle function in middle-aged adults (n = 19; age ± SEM: 52 ± 1 y) in response to leucine supplementation (LEU group: 0.06 g â kg(-1) â meal(-1)) or an alanine control (CON group) during 14 d of bed rest. RESULTS: Bed rest decreased postabsorptive MPS by 30% ± 9% (CON group) and by 10% ± 10% (LEU group) (main effect for time, P < 0.05), but no differences between groups with respect to pre-post changes (group × time interactions) were detected for MPS or cell signaling. Leucine protected knee extensor peak torque (CON compared with LEU group: -15% ± 2% and -7% ± 3%; group × time interaction, P < 0.05) and endurance (CON compared with LEU: -14% ± 3% and -2% ± 4%; group × time interaction, P < 0.05), prevented an increase in body fat percentage (group × time interaction, P < 0.05), and reduced whole-body lean mass loss after 7 d (CON compared with LEU: -1.5 ± 0.3 and -0.8 ± 0.3 kg; group × time interaction, P < 0.05) but not 14 d (CON compared with LEU: -1.5 ± 0.3 and -1.0 ± 0.3 kg) of bed rest. Leucine also maintained muscle quality (peak torque/kg leg lean mass) after 14 d of bed-rest inactivity (CON compared with LEU: -9% ± 2% and +1% ± 3%; group × time interaction, P < 0.05). CONCLUSIONS: Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively brief periods of physical inactivity. This trial was registered at clinicaltrials.gov as NCT00968344.