title: Raised FGF-21 and Triglycerides Accompany Increased Energy Intake Driven by Protein Leverage in Lean, Healthy Individuals: A Randomised Trial.
abstract: A dominant appetite for protein drives increased energy intake in humans when the proportion of protein in the diet is reduced down to approximately 10% of total energy. Compensatory feeding for protein is apparent over a 1–2 d period but the mechanisms driving this regulation are not fully understood. Fibroblast growth factor-21 (FGF-21) has been identified as a candidate protein signal as levels increase in the circulation when dietary protein is low. The aim of this randomised controlled trial was to assess whether changes in percent dietary protein over a 4 d ad libitum experimental period in lean, healthy participants influenced energy intake, metabolic health, circulating FGF-21 and appetite regulating hormones including ghrelin, glucagon like peptide-1 and cholecystokinin. Twenty-two lean, healthy participants were fed ad libitum diets containing 10, 15 and 25% protein, over three, 4 d controlled, in-house experimental periods. Reduced dietary protein intake from 25% to 10% over a period of 4 d was associated with 14% increased energy intake (p = 0.02) as previously reported, and a 6-fold increase in fasting circulating plasma FGF-21 levels (p<0.0001), a 1.5-fold increase in serum triglycerides (p<0.0001), and a 0.9-fold decrease in serum total cholesterol (p = 0.02). Serum HDL cholesterol was reduced with a reduction in dietary protein from 15% to 10% (p = 0.01) over 4 d but not from 25% to 10% (p = 0.1) and the change from baseline was not different between diets. Plasma fasting insulin levels following the 4 d study period were significantly lower following the 25% ad libitum study period compared to the 15% protein period (p = 0.014) but not the 10% protein period (p = 0.2). Variability in interstitial glucose during each study period increased with a decrease in dietary protein from 25% to 15% and 10% (p = 0.001 and p = 0.04, respectively). Ghrelin, glucagon-like peptide-1 and cholecystokinin were unchanged. Increases in energy intake, plasma FGF-21 and serum triglycerides were associated with reductions in percent dietary protein from 25% to 10% energy over a 4 d ad libitum in-house feeding period and may be important in regulation of dietary protein intake.
  
  
  
  Australia New Zealand Clinical Trials Registry ACTRN12616000144415.
authors.affiliation: Charles Perkins Centre D17, The University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Alison K
authors.initials: AK
authors.lastname: Gosby
authors.affiliation: Charles Perkins Centre D17, The University of Sydney, Sydney, New South Wales, Australia.|Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Namson S
authors.initials: NS
authors.lastname: Lau
authors.affiliation: Charles Perkins Centre D17, The University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.|Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Charmaine S
authors.initials: CS
authors.lastname: Tam
authors.affiliation: School of Health Sciences, University of Tasmania, Darlinghurst Campus, Darlinghurst, New South Wales, Australia.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Iglesias
authors.affiliation: Pennington Biomedical Research Centre (PBRC), Baton Rouge, Louisiana, United States of America.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Morrison
authors.affiliation: Charles Perkins Centre D17, The University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.|Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Caterson
authors.affiliation: Charles Perkins Centre D17, The University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.|Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jennie
authors.initials: J
authors.lastname: Brand-Miller
authors.affiliation: Charles Perkins Centre D17, The University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Conigrave
authors.affiliation: Charles Perkins Centre D17, The University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.|School of Veterinary Science, The University of Sydney, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Raubenheimer
authors.affiliation: Charles Perkins Centre D17, The University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Simpson
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002766:Cholecystokinin / Q000097:blood; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D002149:Energy Intake / Q000502:physiology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D054439:Ghrelin / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004044:Dietary Proteins; D054439:Ghrelin; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin