Time-restricted feeding prevents metabolic diseases through the regulation of galanin/GALR1 expression in the hypothalamus of mice

Purpose: Time-restricted feeding (TRF) reverses obesity and insulin resistance, yet the central mechanisms underlying its beneficial effects are not fully understood. Recent studies suggest a critical role of hypothalamic galanin and its receptors in the regulation of energy balance. It is yet unclear whether TRF could regulate the expression of galanin and its receptors in the hypothalamus of mice fed a high-fat diet.

Methods: To test this effect, we subjected mice to either ad lib or TRF of a high-fat diet for 8 h per day. After 4 weeks, galanin and many neuropeptides associated with the function of metabolism were examined.

Results: The present findings showed that mice under TRF consume equivalent calories from a high-fat diet as those with ad lib access, yet are protected against obesity and have improved glucose metabolism. Plasma galanin, orexin A, irisin and adropin levels were significantly reversed by TRF regimen. Besides, TRF regimen reversed the progression of metabolic disorders in mice by increasing GLUT4 and PGC-1α expression in skeletal muscles. Moreover, the levels of galanin and GALR1 expression were severely diminished in the hypothalamus of the TRF mice, whereas GALR2 was highly expressed.

Conclusions: TRF diminished galanin and GALR1 expression, and increased GALR2 expression in the hypothalamus of mice fed a high-fat diet. The current studies provide additional evidence that TRF is effective in improving HFD-induced hyperglycemia and insulin resistance in mice, and this effect could be associated with TRF-induced changes of the galanin systems in the hypothalamus.

Level of evidence: No level of evidence, animal studies.