Impact of leucine on energy balance

McAllan, Liam; Cotter, Paul D.; Roche, Helen M.; Korpela, Riitta; Nilaweera, Kanishka N.

doi:10.1007/s13105-012-0170-2

Cited by 33 publications

(21 citation statements)

References 73 publications

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“…A longer duration of WPI intake (21 weeks) was found to significantly increase the adipose tissue expression of β-3AR compared with that of the control HFD group ( 57 ) . These data suggest the possibility that WPI increases lipolysis in adipocytes via the activation of β-3AR, possibly arising as a consequence of the effects of dietary protein on the central nervous system, given that central nervous system outflow to the adipose tissue activates β-3AR ( 37 , 38 , 58 , 59 ) .…”

Section: Discussionmentioning

confidence: 86%

Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes

et al. 2013

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The intake of whey protein isolate (WPI) is known to reduce high-fat diet (HFD)-induced body-weight gain and adiposity. However, the molecular mechanisms are not fully understood. To this end, we fed C57BL/6J mice for 8 weeks with diets containing 10 % energy as fat (low-fat diet, LFD) or 45 % energy as fat (HFD) enriched with either 20 % energy as casein (LFD and HFD) or WPI (high-fat WPI). Metabolic parameters and the hypothalamic and epididymal adipose tissue expression of energy balance-related genes were investigated. The HFD increased fat mass and plasma leptin levels and decreased the dark-phase energy intake, meal number, RER, and metabolic (VO 2 and heat) and locomotor activities compared with the LFD. The HFD increased the hypothalamic tissue mRNA expression of the leptin receptor, insulin receptor (INSR) and carnitine palmitoyltransferase 1b (CPT1b). The HFD also reduced the adipose tissue mRNA expression of GLUT4 and INSR. In contrast, WPI reduced fat mass, normalised dark-phase energy intake and increased meal size in HFD-fed mice. The dietary protein did not have an impact on plasma leptin, insulin, glucose or glucagon-like peptide 1 levels, but increased plasma TAG levels in HFD-fed mice. At a cellular level, WPI significantly reduced the HFD-associated increase in the hypothalamic tissue mRNA expression of the leptin receptor, INSR and CPT1b. Also, WPI prevented the HFD-induced reduction in the adipose tissue mRNA expression of INSR and GLUT4. In comparison with casein, the effects of WPI on energy intake and hypothalamic and adipose tissue gene expression may thus represent a state of reduced susceptibility to weight gain on a HFD.

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Section: Discussionmentioning

confidence: 86%

Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes

et al. 2013

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“…Interestingly, Zhang et al [64] showed that HFD fed mice on leucine-supplemented drinking water have reduced fasting plasma levels of aspartic acid, glutamic acid, and phenylalanine, as well as increased VO 2 and reduced adiposity compared to HFD controls. Given the influence of leucine on WPI-induced muscle hypertrophy [65], [66] and its unique ability to regulate the translation of protein synthesis [67], it is possible that the elevated leucine content found normally in the WPI diets may have enhanced muscle protein synthesis by directing other amino acids towards protein synthesis and/or catabolism [68], [69], with the required energy been derived possibly from fat catabolism [70]. Consistent with the latter suggestion, we found an increased lean mass and a trend towards a reduction in fat mass with decreased plasma levels of several amino acids, but not leucine, when the casein protein in a HFD was replaced with WPI or when the P/C ratio in the HFD was increased.…”

Section: Discussionmentioning

confidence: 99%

Protein Quality and the Protein to Carbohydrate Ratio within a High Fat Diet Influences Energy Balance and the Gut Microbiota In C57BL/6J Mice

et al. 2014

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Macronutrient quality and composition are important determinants of energy balance and the gut microbiota. Here, we investigated how changes to protein quality (casein versus whey protein isolate; WPI) and the protein to carbohydrate (P/C) ratio within a high fat diet (HFD) impacts on these parameters. Mice were fed a low fat diet (10% kJ) or a high fat diet (HFD; 45% kJ) for 21 weeks with either casein (20% kJ, HFD) or WPI at 20%, 30% or 40% kJ. In comparison to casein, WPI at a similar energy content normalised energy intake, increased lean mass and caused a trend towards a reduction in fat mass (P = 0.08), but the protein challenge did not alter oxygen consumption or locomotor activity. WPI reduced HFD-induced plasma leptin and liver triacylglycerol, and partially attenuated the reduction in adipose FASN mRNA in HFD-fed mice. High throughput sequence-based analysis of faecal microbial populations revealed microbiota in the HFD-20% WPI group clustering closely with HFD controls, although WPI specifically increased Lactobacillaceae/Lactobacillus and decreased Clostridiaceae/Clostridium in HFD-fed mice. There was no effect of increasing the P/C ratio on energy intake, but the highest ratio reduced HFD-induced weight gain, fat mass and plasma triacylglycerol, non-esterified fatty acids, glucose and leptin levels, while it increased lean mass and oxygen consumption. Similar effects were observed on adipose mRNA expression, where the highest ratio reduced HFD-associated expression of UCP-2, TNFα and CD68 and increased the diet-associated expression of β3-AR, LPL, IR, IRS-1 and GLUT4. The P/C ratio also impacted on gut microbiota, with populations in the 30/40% WPI groups clustering together and away from the 20% WPI group. Taken together, our data show that increasing the P/C ratio has a dramatic effect on energy balance and the composition of gut microbiota, which is distinct from that caused by changes to protein quality.

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“…The leucine sensing structures are located in the mediobasal hypothalamus (including the arcuate and ventromedial nuclei) and the dorsal vagal complex of the caudal brainstem (including the nucleus of the solitary tract, the dorsal motor vagus and the area postrema). In these brain areas, leucine induces neurons to express the anorexigenic proopiomelanocortin (POMC) that reduces feeding and body weight gain (McAllan et al, ) (Figure ).…”

Section: Branched‐chain Amino Acid Pharmacodynamicsmentioning

confidence: 99%

Branched‐chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view

Bifari

Nisoli

2016

British J Pharmacology

113

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Substantial evidence has been accumulated suggesting that branched-chain amino acid (BCAA) supplementation or BCAA-rich diets have a positive effect on the regulation of body weight, muscle protein synthesis, glucose homeostasis, the ageing process and extend healthspan. Despite these beneficial effects, epidemiological studies have shown that BCAA plasma concentrations and BCAA metabolism are altered in several metabolic disorders, including type 2 diabetes mellitus and cardiovascular diseases. In this review article, we present an overview of the current literature on the different effects of BCAAs in health and disease. We also highlight the results showing the most promising therapeutic effects of dietary BCAA supplementation and discuss how BCAAs can trigger different and even opposite effects, depending on the catabolic and anabolic states of the organisms. Moreover, we consider the effects of BCAAs when metabolism is abnormal, in the presence of a mixture of different anabolic and catabolic signals. These unique pharmacodynamic properties may partially explain some of the markedly different effects found in BCAA supplementation studies. To predict accurately these effects, the overall catabolic/anabolic status of patients should be carefully considered. In wider terms, a correct modulation of metabolic disorders would make nutraceutical interventions with BCAAs more effective. LINKED ARTICLESThis article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc Abbreviations ALS, amyotrophic lateral sclerosis; BCAA, branched-chain amino acid; BCAT, BCAA aminotransferase; BCKA, branchedchain α-keto acid; BCKDC, BCK dehydrogenase complex; EAA, essential amino acid; eNOS, endothelial NOS; GATOR, GAP activity towards rags; GCN2, general amino acid control non-derepressible 2; GLP-1, glucagon-like peptide-1; 3-HIB, 3-hydroxyisobutyrate; IRS-1, insulin receptor substrate 1; mTORC1, mammalian/mechanistic target of rapamycin complex 1; PGC-1α, PPARγ coactivator-1α; PDH, pyruvate dehydrogenase complex; PP2Cm, mitochondrial-targeted 2C-type Ser/Thr protein phosphatase; T2DM, type 2 diabetes mellitus; tRNA, transfer RNA; WAT, white adipose tissue

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Impact of leucine on energy balance

Cited by 33 publications

References 73 publications

Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes

Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes

Protein Quality and the Protein to Carbohydrate Ratio within a High Fat Diet Influences Energy Balance and the Gut Microbiota In C57BL/6J Mice

Branched‐chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view

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