Low-protein diet-induced hyperphagia and adiposity are modulated through interactions involving thermoregulation, motor activity, and protein quality in mice

Blais, Anne; Chaumontet, Catherine; Azzout‐Marniche, Dalila; Piedcoq, Julien; Fromentin, Gilles; Gaudichon, Claire; Tomé, Daniel; Even, Patrick C.

doi:10.1152/ajpendo.00318.2017

Cited by 28 publications

(40 citation statements)

References 42 publications

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“…Here, we show that the 5AA diets induced hyperphagia, which was generally similar to previous reports showing that protein-diluted diets promote hyperphagia in rats, mice, and humans [8,9,10,11,12,52]. Since the initial increase in the food intake of 5AA+Met was comparable to 5AA, it suggests that methionine supplementation alone was insufficient to partially reverse the hyperphagic response to protein dilution.…”

Section: Discussionsupporting

confidence: 91%

“…The enhanced energy expenditure with the 5AA, 5AA+Met, and V-16AA-Met diets was consistent with the increased energy expenditure resulting from dietary protein dilution [8,14,15,16,17,18,52] or with methionine restriction [13,30,31,32,58] in rodents. The underlying mechanisms by which total AA restriction or methionine restriction increase energy expenditure are not completely understood.…”

Section: Discussionsupporting

confidence: 61%

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Methionine Restriction Partly Recapitulates the Sympathetically Mediated Enhanced Energy Expenditure Induced by Total Amino Acid Restriction in Rats

et al. 2019

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Total amino acid (AA) restriction promotes hyperphagia and energy expenditure. We determined whether (i) methionine restriction mimics the effects of total AA restriction, (ii) methionine supplementation attenuates these responses, and iii) sympathetic signaling mediates such effects. Rats were injected with either vehicle (V) or 6-hydroxydopamine (S) to induce chemical sympathectomy, and then randomized to four diets: 16% AA (16AA), 5% AA (5AA), 16% AA-methionine (16AA-Met), and 5% AA+methionine (5AA+Met). Propranolol or ondansetron were injected to examine the role of sympathetic and serotonergic signaling, respectively. 5AA, 5AA+Met, and 16AA-Met increased the food conversion rate for 1–3 weeks in the V and S groups, and increased mean energy expenditure in V group,; the magnitude of these changes was attenuated in the S group. Propranolol decreased the energy expenditure of V16AA, V5AA, and V5AA+Met and of S5AA, S5AA+Met, and S16AA-Met, whereas ondansetron decreased the energy expenditure in only the S groups. Compared to 16AA, the other V groups had reduced body weights from days 7–11 onwards and decreased lean masses throughout the study and the other S groups had decreased body weights and lean masses from day 14 onwards. Total AA restriction enhanced the energy expenditure and reduced the weight and lean mass; these effects were partly recapitulated by methionine restriction and were sympathetically mediated.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 61%

Methionine Restriction Partly Recapitulates the Sympathetically Mediated Enhanced Energy Expenditure Induced by Total Amino Acid Restriction in Rats

et al. 2019

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“…The authors and others reported that mild protein restriction increases caloric intake in rodents and in some, but not in all human studies . Most studies assessing the effects of protein restriction on energy balance formulated isocaloric diets by substituting protein with carbohydrate, while keeping fat concentration constant;; whether the hyperphagic and metabolic responses to protein restriction are due to a reciprocal increase in carbohydrate content is largely unknown. In a recent meta‐analysis of 24 studies on rodents, diets high in carbohydrate but with adequate protein had no effect on calorie intake .…”

Section: Introductionmentioning

confidence: 99%

Low‐Protein Diets with Fixed Carbohydrate Content Promote Hyperphagia and Sympathetically Mediated Increase in Energy Expenditure

Zapata

Singh

Pezeshki

et al. 2019

Molecular Nutrition Food Res

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Scope: Dietary protein restriction elicits hyperphagia and increases energy expenditure; however, less is known of whether these responses are a consequence of increasing carbohydrate content. The effects of protein-diluted diets with fixed carbohydrate content on energy balance, hormones, and key markers of protein sensing and thermogenesis in tissues are determined. Methods and results: Obesity-prone rats (n = 13-16 per group) are randomized to diets containing fixed carbohydrate (52% calories) and varying protein concentrations: 15% (control), 10% (mild protein restriction), 5% (moderate protein restriction) or 1% (severe protein restriction) protein calories, or protein-matched to 5% protein, for 21 days. Propranolol and ondansetron are administered to interrogate the roles of sympathetic and serotonergic systems, respectively, in diet-induced changes in energy expenditure. It is found that mild-to-moderate protein restriction promotes transient hyperphagia, whereas severe protein restriction induces hypophagia, with alterations in meal patterns. Protein restriction enhances energy expenditure that is partly attenuated by propranolol, but not ondansetron. Moderate to severe protein restriction decreases gains in body weight, lean and fat mass, decreased postprandial glucose and leptin, but increased fibroblast growth factor-21 concentrations. Protein-matching retains lean mass suggesting that intake of dietary protein, but not calories, is important for preserving lean mass. Notably, protein restriction increases the protein and/or transcript abundance of key amino acid sensing molecules in liver and intestine (PERK, eIF2α, ATF2, CHOP, 4EBP1, FGF21), and upregulated thermogenic markers (β2AR, Klotho, HADH, UCP-1) in brown adipose tissue. Conclusion: Low-protein diets promote hyperphagia and sympathetically mediated increase in energy expenditure, prevent gains in tissue reserves, and concurrently upregulate hepatic and intestinal amino acid sensing intermediaries and thermogenic markers in brown adipose tissue.

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“…However, the systems responsible for integrating nutrient status and macronutrient preference to prevent nutrient excess or deficiency are only recently becoming clear. For example, under conditions of amino acid restriction, mammals will increase intake of low protein diets to achieve physiologically necessary levels of dietary protein 2,3 , a phenomenon termed "the protein leverage effect" [4][5][6][7][8][9][10] . This increase in food intake arising from restriction of amino acids results in a coordinated increase in energy expenditure, likely to offset increased caloric intake and maintain body weight homeostasis.…”

mentioning

confidence: 99%

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

Flippo

Jensen-Cody

Claflin

et al. 2020

Sci Rep

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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 β-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, β-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.

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Low-protein diet-induced hyperphagia and adiposity are modulated through interactions involving thermoregulation, motor activity, and protein quality in mice

Cited by 28 publications

References 42 publications

Methionine Restriction Partly Recapitulates the Sympathetically Mediated Enhanced Energy Expenditure Induced by Total Amino Acid Restriction in Rats

Methionine Restriction Partly Recapitulates the Sympathetically Mediated Enhanced Energy Expenditure Induced by Total Amino Acid Restriction in Rats

Low‐Protein Diets with Fixed Carbohydrate Content Promote Hyperphagia and Sympathetically Mediated Increase in Energy Expenditure

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

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