Dataset Information

FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution.

ABSTRACT: Alterations in macronutrient intake can have profound effects on energy intake and whole-body metabolism. For example, reducing protein intake increases energy expenditure, increases insulin sensitivity and decreases body weight in rodents. Fibroblast growth factor 21 (FGF21) signaling in the brain is necessary for the metabolic effects of dietary protein restriction and has more recently been proposed to promote protein preference. However, the neuron populations through which FGF21 elicits these effects are unknown. Here, we demonstrate that deletion of ?-klotho in glutamatergic, but not GABAergic, neurons abrogated the effects of dietary protein restriction on reducing body weight, but not on improving insulin sensitivity in both diet-induced obese and lean mice. Specifically, FGF21 signaling in glutamatergic neurons is necessary for protection against body weight gain and induction of UCP1 in adipose tissues associated with dietary protein restriction. However, ?-klotho expression in glutamatergic neurons was dispensable for the effects of dietary protein restriction to increase insulin sensitivity. In addition, we report that FGF21 administration does not alter protein preference, but instead promotes the foraging of other macronutrients primarily by suppressing simple sugar consumption. This work provides important new insights into the neural substrates and mechanisms behind the endocrine control of metabolism during dietary protein dilution.

SUBMITTER: Flippo KH

PROVIDER: S-EPMC7658965 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution.

Flippo Kyle H KH Jensen-Cody Sharon O SO Claflin Kristin E KE Potthoff Matthew J MJ

Scientific reports 20201111 1

Alterations in macronutrient intake can have profound effects on energy intake and whole-body metabolism. For example, reducing protein intake increases energy expenditure, increases insulin sensitivity and decreases body weight in rodents. Fibroblast growth factor 21 (FGF21) signaling in the brain is necessary for the metabolic effects of dietary protein restriction and has more recently been proposed to promote protein preference. However, the neuron populations through which FGF21 elicits the ...[more]

PMID: 33177640

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Project description:Although the 'Low-Fat' diet was the predominant public health recommendation for weight loss and weight control for the past several decades, the obesity epidemic continued to grow during this time period. An alternative 'low-carbohydrate' (Low-Carb) approach, although originally dismissed and even vilified, was comparatively tested in a series of studies over the past decade, and has been found in general to be as effective, if not more, as the Low-Fat approach for weight loss and for several related metabolic health measures. From a glass half full perspective, this suggests that there is more than one choice for a dietary approach to lose weight, and that Low-Fat and Low-Carb diets may be equally effective. From a glass half empty perspective, the average amount of weight lost on either of these two dietary approaches under the conditions studied, particularly when followed beyond 1 year, has been modest at best and negligible at worst, suggesting that the two approaches may be equally ineffective. One could resign themselves at this point to focusing on calories and energy intake restriction, regardless of macronutrient distributions. However, before throwing out the half-glass of water, it is worthwhile to consider that focusing on average results may mask important subgroup successes and failures. In all weight-loss studies, without exception, the range of individual differences in weight change within any particular diet groups is orders of magnitude greater than the average group differences between diet groups. Several studies have now reported that adults with greater insulin resistance are more successful with weight loss on a lower-carbohydrate diet compared with a lower-fat diet, whereas adults with greater insulin sensitivity are equally or more successful with weight loss on a lower-fat diet compared with a lower-carbohydrate diet. Other preliminary findings suggest that there may be some promise with matching individuals with certain genotypes to one type of diet over another for increasing weight-loss success. Future research to address the macronutrient intake component of the obesity epidemic should build on these recent insights and be directed toward effectively classifying individuals who can be differentially matched to alternate types of weight-loss diets that maximize weight-loss and weight-control success.

Dataset Information

FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution.

Publications

FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution.

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