Protein quality and the protein to carbohydrate ratio within a high fat diet influences energy balance and the gut microbiota in C57BL/6J mice

PLoS One. 2014 Feb 10;9(2):e88904. doi: 10.1371/journal.pone.0088904. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Amino Acids / blood
  • Animals
  • Body Composition / drug effects
  • Carbohydrate Metabolism* / drug effects
  • Diet, High-Fat*
  • Energy Metabolism* / drug effects
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / microbiology*
  • Gene Expression Regulation / drug effects
  • Hormones / blood
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbiota* / drug effects
  • Milk Proteins / pharmacology
  • Proteins / metabolism*
  • Whey Proteins

Substances

  • Amino Acids
  • Hormones
  • Milk Proteins
  • Proteins
  • Whey Proteins

Grant support

KN is supported by the Teagasc Vision Programme on Obesity, which also funded the work detailed in this manuscript. LM is supported by a Teagasc PhD Walsh Fellowship. HMR is supported by SFI PI (11/PI/1119). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.