Reversing diet-induced metabolic dysregulation by diet switching leads to altered hepatic de novo lipogenesis and glycerolipid synthesis.
In humans, low-energy diets rapidly reduce hepatic fat and improve/normalise glycemic control. Due to difficulties in obtaining human liver, little is known about changes to the lipid species and pathway fluxes that occur under these conditions. Using a combination of stable isotope, and targeted metabolomic approaches we investigated the acute (7-9 days) hepatic effects of switching high-fat high-sucrose diet (HFD) fed obese mice back to a chow diet. Upon the switch, energy intake was reduced, resulting in reductions of fat mass and hepatic triacyl- and diacylglycerol. However, these parameters were still elevated compared to chow fed mice, thus representing an intermediate phenotype. Nonetheless, glucose intolerance and hyperinsulinemia were completely normalized. The diet reversal resulted in marked reductions in hepatic de novo lipogenesis when compared to the chow and HFD groups. Compared with HFD, glycerolipid synthesis was reduced in the reversal animals, however it remained elevated above that of chow controls, indicating that despite experiencing a net loss in lipid stores, the liver was still actively esterifying available fatty acids at rates higher than that in chow control mice. This effect likely promotes the re-esterification of excess free fatty acids released from the breakdown of adipose depots during the weight loss period.
Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia.
Greg M
GM
Kowalski
Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia.
Steven
S
Hamley
Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia.
Ahrathy
A
Selathurai
Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Parkville, Australia.
Joachim
J
Kloehn
Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Parkville, Australia.
David P
DP
De Souza
Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Parkville, Australia.
Sean
S
O'Callaghan
Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Parkville, Australia.
Brunda
B
Nijagal
Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Parkville, Australia.
Dedreia L
DL
Tull
Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Parkville, Australia.
Malcolm J
MJ
McConville
Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia.
Clinton R
CR
Bruce
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage*; D004075:Diglycerides / Q000378:metabolism; D002149:Energy Intake; D005227:Fatty Acids / Q000378:metabolism; D018149:Glucose Intolerance; D006017:Glycolipids / Q000096:biosynthesis*; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain
C011439:1,2-diacylglycerol; D001786:Blood Glucose; D004041:Dietary Fats; D004075:Diglycerides; D005227:Fatty Acids; D006017:Glycolipids; D014280:Triglycerides; C015903:glycerolglycolipids