• Juliet D Gotthardt, Jessica L Verpeut, Bryn L Yeomans, Jennifer A Yang, Ali Yasrebi, Troy A Roepke, and Nicholas T Bello.
• Department of Animal Sciences (J.D.G., J.L.V., B.L.Y., J.A.Y., A.Y., T.A.R., N.T.B.), School of Environmental and Biological Sciences, Nutritional Sciences Graduate Program (J.D.G., B.L.Y., T.A.R., N.T.B.), Graduate Program in Endocrinology and Animal Biosciences (J.L.V., J.A.Y., T.A.R., N.T.B.), and New Jersey Institute for Food, Nutrition, and Health (T.A.R., N.T.B.), Rutgers, The State University of New Jersey, New Brunswick, New Jersey 0890.
• Endocrinology. 2016 Feb 1; 157 (2): 679-91.

AbstractClinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%-52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%-13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%-42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%-60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%-32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%-75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.

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