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JMG, Humans, Mice, Animals, Sucrose, Agouti-Related Protein, Mice, Inbred C57BL, Obesity, Weight Gain, Diet, High-Fat, Neurons, Water, Body Weight

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Int J Obes (Lond). 2023;47:224-35







This work was supported by F32 DK120298 (ACK, KMSO), R01 DK102918 (KMSO), RF1 AG059778 (CCK, KMSO) and the National Research Council for the Scientific and Technologic Development of Brasil (CNPq – Brazil) (KOA, JHLC).


BACKGROUND/OBJECTIVE: As the obesity epidemic continues, the understanding of macronutrient influence on central nervous system function is critical for understanding diet-induced obesity and potential therapeutics, particularly in light of the increased sugar content in processed foods. Previous research showed mixed effects of sucrose feeding on body weight gain but has yet to reveal insight into the impact of sucrose on hypothalamic functioning. Here, we explore the impact of liquid sucrose feeding for 12 weeks on body weight, body composition, caloric intake, and hypothalamic AgRP neuronal function and synaptic plasticity.

METHODS: Patch-clamp electrophysiology of hypothalamic AgRP neurons, metabolic phenotyping and food intake were performed on C57BL/6J mice.

RESULTS: While mice given sugar-sweetened water do not gain significant weight, they do show subtle differences in body composition and caloric intake. When given sugar-sweetened water, mice show similar alterations to AgRP neuronal excitability as in high-fat diet obese models. Increased sugar consumption also primes mice for increased caloric intake and weight gain when given access to a HFD.

CONCLUSIONS: Our results show that elevated sucrose consumption increased activity of AgRP neurons and altered synaptic excitability. This may contribute to obesity in mice and humans with access to more palatable (HFD) diets.


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