Short‐term protein restriction at advanced age stimulates FGF21 signalling, energy expenditure and browning of white adipose tissue

Dommerholt, Marleen B; Blankestijn, Maaike; Vieira-Lara, Marcel A.; Dijk, Theo H. van; Wolters, Henk; Koster, Mirjam H.; Gerding, Albert; Os, Ronald P. van; Bloks, Vincent W.; Bakker, Barbara M.; Kruit, Janine K.; Jonker, Johan W.

doi:10.1111/febs.15604

Cited by 22 publications

(32 citation statements)

References 72 publications

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“…Although hepatic FGF21 seems to stimulate BAT thermogenesis via an endocrine pathway ( 29 , 30 , 36 , 74 , 89 ), the FGF21 expression and secretion in BAT is also increased by sympathetic stimulation ( 72 , 90 ). We and others showed that plasma FGF21 concentrations and transcripts in liver, small intestine, skeletal muscle and BAT were increased when rodents are fed with low protein diets ( 27 , 31 , 36 , 53 , 60 , 75 , 91 ). Further, methionine and leucine restriction increases FGF21 expression particularly in liver and circulation ( 92 – 94 ).…”

Section: Regulation Of Energy Expenditure By Low Protein Dietsmentioning

confidence: 89%

“…Likewise, others have shown that low protein induced EE occurs independent of hyperphagia ( 35 ) and that energy intake changes as a secondary response to compensate for the enhanced EE ( 70 ). Therefore, it appears that increased EE in response to protein restriction is partly related to enhanced basal metabolic rate component of total EE ( 53 ), although the contribution of basal metabolic rate and diet-induced thermogenesis was reported to be negligible ( 71 ). An increased spontaneous motor activity was reported in mice fed with low protein diets ( 71 ), which does not seem to be related with the overall activity level ( 69 , 71 ).…”

Section: Regulation Of Energy Expenditure By Low Protein Dietsmentioning

confidence: 99%

“…Due to high carbohydrate content of low protein diets ( 13 , 14 , 27 , 48 , 49 , 51 , 53 – 56 , 60 , 61 ) an increased EE in response to such diets could be the result of either high carbohydrate or low protein content. In an independent study, using obesity-prone rats we showed that low protein diets with fixed carbohydrate, but variable fat contents increased EE ( 31 ), similar to low protein-high carbohydrate diets ( 27 ).…”

Section: Regulation Of Energy Expenditure By Low Protein Dietsmentioning

confidence: 99%

“…Fibroblast growth factor-21 is released in response to nutrient deficiency and stimulates browning of white adipose tissue to regulate adaptive thermogenesis ( 53 , 74 ). Infusion of FGF21 increases EE and core body temperature in rodent models ( 84 – 86 ).…”

Section: Regulation Of Energy Expenditure By Low Protein Dietsmentioning

confidence: 99%

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Low Protein Diets and Energy Balance: Mechanisms of Action on Energy Intake and Expenditure

Pezeshki

Chelikani

2021

Front. Nutr.

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Low protein diets are associated with increased lifespan and improved cardiometabolic health primarily in rodents, and likely improve human health. There is strong evidence that moderate to severe reduction in dietary protein content markedly influences caloric intake and energy expenditure, which is often followed by a decrease in body weight and adiposity in animal models. While the neuroendocrine signals that trigger hyperphagic responses to protein restriction are better understood, there is accumulating evidence that increased sympathetic flux to brown adipose tissue, fibroblast growth factor-21 and serotonergic signaling are important for the thermogenic effects of low protein diets. This mini-review specifically focuses on the effect of low protein diets with variable carbohydrate and lipid content on energy intake and expenditure, and the underlying mechanisms of actions by these diets. Understanding the mechanisms by which protein restriction influences energy balance may unveil novel approaches for treating metabolic disorders in humans and improve production efficiency in domestic animals.

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Section: Regulation Of Energy Expenditure By Low Protein Dietsmentioning

confidence: 89%

Section: Regulation Of Energy Expenditure By Low Protein Dietsmentioning

confidence: 99%

Section: Regulation Of Energy Expenditure By Low Protein Dietsmentioning

confidence: 99%

Section: Regulation Of Energy Expenditure By Low Protein Dietsmentioning

confidence: 99%

See 2 more Smart Citations

Low Protein Diets and Energy Balance: Mechanisms of Action on Energy Intake and Expenditure

Pezeshki

Chelikani

2021

Front. Nutr.

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“…1A: detailed timeline. Energy expenditure (EE), respiratory exchange ratio (RER) and measurements from blood samples were performed as described elsewhere (22).…”

Section: Introductionmentioning

confidence: 99%

Age-related susceptibility to insulin resistance is due to a combination of CPT1B decline and lipid overload

Vieira-Lara

Dommerholt

Zhang

et al. 2021

Preprint

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BACKGROUND: Advanced age increases the susceptibility to diet-induced insulin resistance (IR). A key driver of this phenomenon is lipid accumulation in the skeletal muscle. It is debated, however, whether this is due to dietary lipid overload or decline of mitochondrial function. To address the interplay of diet and age in the flexibility of muscle lipid and glucose handling, we put young and aged mice on a low- or high-fat diet (HFD). RESULTS: As expected, aged mice were more susceptible to IR when given a HFD than young mice. The HFD induced intramuscular lipid accumulation specifically in aged mice, including C18:0-containing ceramides and diacylglycerols. This was reflected by the mitochondrial β-oxidation capacity, which was upregulated by the HFD in young, but not in old mice. Conspicuously, most β-oxidation proteins were upregulated by the HFD in both groups, but carnitine palmitoyltransferase 1B (CPT1B) declined in aged animals. Computational modelling traced the flux control mostly to CPT1B, suggesting a CPT1B-driven loss of flexibility to the HFD with age. Finally, in old animals glycolytic protein levels were reduced and less flexible to the diet. CONCLUSION: We conclude that intramuscular lipid accumulation and decreased insulin sensitivity are not due to age-related mitochondrial dysfunction or nutritional overload alone, but rather to their interaction. Moreover, we identify CPT1B as a potential target to counteract age-dependent intramuscular lipid accumulation and thereby IR.

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Protein Restriction in Aging and Disease

Brandhorst

2024

Intermittent and Periodic Fasting, Aging and Disease

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Short‐term protein restriction at advanced age stimulates FGF21 signalling, energy expenditure and browning of white adipose tissue

Cited by 22 publications

References 72 publications

Low Protein Diets and Energy Balance: Mechanisms of Action on Energy Intake and Expenditure

Low Protein Diets and Energy Balance: Mechanisms of Action on Energy Intake and Expenditure

Age-related susceptibility to insulin resistance is due to a combination of CPT1B decline and lipid overload

Protein Restriction in Aging and Disease

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