At similar weight loss, dietary composition determines the degree of glycemic improvement in diet-induced obese C57BL/6 mice

Research output: Contribution to journalArticle


BACKGROUND: Achieving weight loss is the cornerstone of the treatment of the metabolic consequences of obesity, in particular of glucose intolerance.

OBJECTIVE: To determine whether improvement in glucose control depends on dietary macronutrient composition of the diet at identical weight loss.

MATERIALS AND METHODS: Twenty-two weeks old diet-induced obese C57BL/6 mice lost weight through caloric restriction on normal chow (R-NC) or high fat diet (R-HF). Control mice were fed normal chow (LEAN) or high fat diet (OBESE) ad libitum. Body weight and composition were assessed after 8 weeks of dietary intervention. Glucose homeostasis was evaluated by intraperitoneal glucose tolerance tests (IPGTT). Epididymal white adipose (eWAT) and hepatic tissues were analyzed by immunohistochemistry and RT-qPCR.

RESULTS: By 30 weeks of age, the body weight of the mice on R-NC (31.6±1.7g, mean±SEM) and R-HF (32.3±0.9g) was similar to LEAN mice (31.9±1.4g), while OBESE mice weighed 51.7±2.4g. Glucose tolerance in R-NC was better than in LEAN mice (69% AUC IPGTT, P 0.0168) whereas R-HF mice remained significantly less glucose tolerant (125% AUC IPGTT, P 0.0279 vs LEAN), despite identical weight loss. The eWAT pads and adipocyte size were similar in LEAN and R-NC mice, while the eWAT pad size of R-HF was 180% of R-NC (P < 0.0001) and the average adipocyte size of R-HF mice was 134% of R-NC fed mice (P 0.0285). No LEAN or R-NC mice had hepatic steatosis, in contrast to 28.6% of R-HF mice. Compared to OBESE mice, inflammatory markers were lower in eWAT and liver tissue of R-NC, but not in R-HF mice. Measures of visceral adiposity correlated well with glucose tolerance parameters.

CONCLUSIONS: In mice, caloric restriction on a normal chow diet improved glucose tolerance significantly more when identical weight loss was achieved on a high fat diet.


  • Roman Vangoitsenhoven
  • Miranda van der Ende
  • Katrien Corbeels
  • João Paulo Monteiro Carvalho Mori Cunha
  • Matthias Lannoo
  • Pierre Bedossa
  • Schalk van der Merwe
  • Ann Mertens
  • Ina Gesquiere
  • Ann Meulemans
  • Christophe Matthys
  • Chantal Mathieu
  • Lut Overbergh
  • Bart Van der Schueren
External organisations
  • University Hospitals Leuven
  • Catholic University of Leuven
  • Paris Diderot University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • Adipocytes/metabolism, Adipose Tissue/metabolism, Adipose Tissue, White/metabolism, Adiposity, Animals, Blood Glucose/metabolism, Body Composition, Body Weight, Caloric Restriction, Calorimetry, Diet, High-Fat, Dietary Fats/metabolism, Eating, Fatty Liver/metabolism, Glucose/chemistry, Glucose Intolerance/metabolism, Homeostasis, Inflammation, Male, Mice, Mice, Inbred C57BL, Mice, Obese/genetics, Nutrients/chemistry, Obesity/metabolism, Weight Loss
Original languageEnglish
Article numbere0200779
Pages (from-to)1-16
JournalPLoS ONE
Issue number7
Publication statusPublished - 2018
Publication categoryResearch
Externally publishedYes