Whey Protein Reduces Early Life Weight Gain in Mice Fed a High-Fat Diet

Tranberg, Britt; Hellgren, Lars; Lykkesfeldt, Jens; Sejrsen, K.; Jeamet, Aymeric; Rune, Ida; Ellekilde, Merete; Nielsen, Dennis Sandris; Hansen, Axel Kornerup

doi:10.1371/journal.pone.0071439

Cited by 42 publications

(41 citation statements)

References 32 publications

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“…In the epididymal adipose tissue, WPI prevented the HFD-induced FASN gene expression, albeit a recent study reported that WPI does not affect the weight of the epididymal tissue in HFD fed mice, but instead causes a reduction in subcutaneous fat pad weight [20]. These data suggest that WPI affects cellular activity in the liver and in specific adipose tissue depots.…”

Section: Discussionmentioning

confidence: 86%

“…A study by Sprong et al, [19] demonstrated that in comparison to casein, whey protein intake increased levels of lactobacilli and bifidobacteria in a rat model of colitis. However, in a more recent study, whey protein intake was found to have no influence on gut microbiota composition in mice fed a HFD for 7 or 13 weeks [20]. Several key unanswered questions are; could whey proteins specifically influence the gut microbiota composition associated with prolonged high fat feeding, and would any changes relate to energy balance?…”

Section: Introductionmentioning

confidence: 97%

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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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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 97%

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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“…41 Fermentation of protein has also been suggested to result in the production of various potentially toxic products, such as amines and ammonia (NH 3 ), and in one report, with growth of potential pathogens 42. In contrast, feeding of whey protein to mice mediates against the negative effects of a high fat diet 43 44. Indeed, in athletes, whey protein supplements represented a significant component of the protein intake in athletes but not controls.…”

Section: Discussionmentioning

confidence: 99%

Exercise and associated dietary extremes impact on gut microbial diversity

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Murphy

O'Sullivan

et al. 2014

Gut

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“…Our data are in agreement with other studies feeding high fat casein or whey diets to mice. 10−12 Gene expression analyses of white and brown adipose tissues as well as skeletal muscle did not support the fact that the reduced lipid deposition was associated with increased dissipation of energy in the form of heat. Moreover, hepatic gene expression analyses and ex vivo hepatic fatty acid oxidation measurements did not support the fact that lipids were differently catabolized in livers of the HF whey and HF-casein-fed mice.…”

Section: Discussionmentioning

confidence: 99%

Urinary Loss of Tricarboxylic Acid Cycle Intermediates As Revealed by Metabolomics Studies: An Underlying Mechanism to Reduce Lipid Accretion by Whey Protein Ingestion?

et al. 2014

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Whey protein intake is associated with the modulation of energy metabolism and altered body composition both in human subjects and in animals, but the underlying mechanisms are not yet elucidated. We fed obesity-prone C57BL/6J mice high-fat diets with either casein (HF casein) or whey (HF whey) for 6 weeks. At equal energy intake and apparent fat and nitrogen digestibility, mice fed HF whey stored less energy as lipids, evident both as lower white adipose tissue mass and as reduced liver lipids, compared with HF-casein-fed mice. Explorative analyses of 48 h urine, both by 1H NMR and LC–MS metabolomic platforms, demonstrated higher urinary excretion of tricarboxylic acid (TCA) cycle intermediates citric acid and succinic acid (identified by both platforms), and cis-aconitic acid and isocitric acid (identified by LC–MS platform) in the HF whey, relative to in the HF-casein-fed mice. Targeted LC–MS analyses revealed higher citric acid and cis-aconitic acid concentrations in fed state plasma, but not in liver of HF-whey-fed mice. We propose that enhanced urinary loss of TCA cycle metabolites drain available substrates for anabolic processes, such as lipogenesis, thereby leading to reduced lipid accretion in HF-whey-fed compared to HF-casein-fed mice.

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Whey Protein Reduces Early Life Weight Gain in Mice Fed a High-Fat Diet

Cited by 42 publications

References 32 publications

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

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

Exercise and associated dietary extremes impact on gut microbial diversity

Urinary Loss of Tricarboxylic Acid Cycle Intermediates As Revealed by Metabolomics Studies: An Underlying Mechanism to Reduce Lipid Accretion by Whey Protein Ingestion?

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