Homeostatic versus hedonic control of carbohydrate selection

• Published in: The Journal of physiology Vol. 598; no. 18; pp. 3831 - 3844
• Main Authors: Minokoshi, Yasuhiko, Nakajima, Ken‐ichiro, Okamoto, Shiki
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2020
• Subjects: Aging; AMP; AMPK; Animals; Carbohydrates; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - metabolism; CRH; Diet; Eating; Fasting; food preference; food selection; High carbohydrate diet; High fat diet; Hypothalamus; Hypothalamus - metabolism; Ketones; Kinases; Mice; Molecular modelling; Neural networks; Neurons; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular nucleus; Physiology; Protein kinase; PVH; Sucrose; CRH; AMPK; PVH; food preference; food selection
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP280066

Macronutrient intake is associated with cardiometabolic health, ageing and longevity, but the mechanisms underlying its regulation have remained unclear. Most rodents increase carbohydrate selection under certain physiological and pathological conditions such as fasting. When presented with a choice between a basally preferable high‐fat diet (HFD) and a high‐carbohydrate diet (HCD) such as a high‐sucrose diet, fasted mice first eat the HFD and then switch to the HCD during the first few hours of refeeding and continue to eat the HCD up to 24 h in the two‐diet choice approach. Such consumption of an HCD after fasting reverses the fasting‐induced increase in the plasma concentration of ketone bodies more rapidly than does refeeding with an HFD alone. 5′‐AMP‐activated protein kinase (AMPK)‐regulated neurons in the paraventricular nucleus of the hypothalamus (PVH) that express corticotropin‐releasing hormone (CRH) are necessary and sufficient for the fasting‐induced selection of carbohydrate over an HFD in mice. These neurons appear to contribute to a fasting‐induced increase in the positive valence of carbohydrate without affecting the preference for more palatable and energy‐dense diets such as an HFD. Identification of the neural circuits in which AMPK‐regulated CRH neurons in the PVH of mice are embedded should shed new light on the physiological and molecular mechanisms responsible for macronutrient selection. figure legend Overnight fasting promotes selection of carbohydrate over fat through activation of AMPK (5′‐AMP‐activated protein kinase)‐regulated CRH (corticotropin‐releasing hormone) neurons in the paraventricular nucleus of the hypothalamus (PVH) in mice. Refeeding with a small amount of a high‐carbohydrate diet (HCD) after fasting results in a decrease in plasma ketone body levels. It may be important that fasting confers a positive valence of carbohydrate because most natural sources of carbohydrate are less palatable than is a high‐fat diet, and AMPK‐regulated CRH neurons in the PVH may mediate this effect of fasting.