Long-term effects of increased protein intake after weight loss on intrahepatic lipid content and implications for insulin sensitivity: a PREVIEW study

Am J Physiol Endocrinol Metab. 2018 Nov 1;315(5):E885-E891. doi: 10.1152/ajpendo.00162.2018. Epub 2018 Aug 7.


The aim of this study was to assess the effects of a weight maintenance period comprising two diets differing in protein intake, after weight loss, on intrahepatic lipid content and implications for insulin sensitivity. A total of 25 participants [body mass index (BMI): 31.1 (3.5 kg/m2; intrahepatic lipid (IHL): 8.7 (8.3%; fasting glucose: 6.4 (0.6 mmol/l; homeostatic model assessment for insulin resistance (HOMA-IR): 3.7 (1.6; Matsuda index: 3.4 (2.9] started an 8-wk low-energy diet followed by a 2-yr weight maintenance period with either high protein or medium protein dietary guidelines. At baseline, after 6 mo, and after 2 yr, IHL, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were determined by magnetic resonance spectroscopy/imaging. Glucose and insulin concentrations, determined during an oral glucose challenge, were used to assess the HOMA-IR and Matsuda insulin sensitivity index (ISI). Protein intake was measured with 24-h urinary nitrogen excretion. Protein intake, BMI, IHL, VAT, SAT, HOMA-IR, and ISI did not change differently between the groups during the intervention. In the whole group, BMI, IHL, VAT, SAT, HOMA-IR, and ISI were favorably changed at 6 mo and 2 yr compared with baseline ( P < 0.05). Mixed-model analysis showed that independent of BMI, protein intake (g/d) at 6 mo was inversely related to IHL (coefficient: -0.04; P < 0.05) and VAT (coefficient: -0.01; P < 0.05). Overall, IHL was positively related to HOMA-IR (coefficient: 0.10; P < 0.01) and inversely related to ISI (coefficient: -0.17; P < 0.01), independent of BMI. A 2-yr medium- to high-protein energy-restricted diet reduced IHL and VAT. Independently of changes in BMI, IHL was inversely related to insulin sensitivity.

Trial registration: ClinicalTrials.gov NCT01777893.

Keywords: body composition; insulin sensitivity; intrahepatic lipid content; protein intake; weight loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Dietary Proteins / metabolism*
  • Female
  • Humans
  • Insulin Resistance / physiology*
  • Intra-Abdominal Fat / metabolism
  • Lipid Metabolism / physiology*
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Obesity / metabolism
  • Weight Loss / physiology*


  • Dietary Proteins

Associated data

  • ClinicalTrials.gov/NCT01777893