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The impacts of different macronutrients on body weight regulation remain unresolved, with different studies suggesting increased dietary fat, increased carbohydrates (particularly sugars), or reduced protein may all stimulate overconsumption and drive obesity. We exposed C57BL/6 mice to 29 different diets varying from 8.3% to 80% fat, 10% to 80% carbohydrate, 5% to 30% protein, and 5% to 30% sucrose. Only increased dietary fat content was associated with elevated energy intake and adiposity. This response was associated with increased gene expression in the 5-HT receptors, and the dopamine and opioid signaling pathways in the hypothalamus. We replicated the core findings in four other mouse strains (DBA/2, BALB/c, FVB, and C3H). Mice regulate their food consumption primarily to meet an energy rather than a protein target, but this system can be over-ridden by hedonic factors linked to fat, but not sucrose, consumption.

Original publication

DOI

10.1016/j.cmet.2018.06.010

Type

Journal article

Journal

Cell Metab

Publication Date

04/09/2018

Volume

28

Pages

415 - 431.e4

Keywords

FGF signaling, energy regulation, fat intake, hedonic overdrive, hypothalamic hunger pathway, mTOR signaling, mice, obesity, protein leverage hypothesis, sucrose intake, Adiposity, Analgesics, Opioid, Animals, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Dopamine, Energy Intake, Hypothalamus, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Obesity, Receptors, Serotonin, Signal Transduction