Author information
1 Wellcome Trust-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Level 4, Box 289, Addenbrooke's Hospital, Cambridge, CB2 0QQ, United Kingdom; The Liver Unit, Department of Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
2 Wellcome Trust-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Level 4, Box 289, Addenbrooke's Hospital, Cambridge, CB2 0QQ, United Kingdom.
3 The Liver Unit, Department of Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
4 Wellcome Trust-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Level 4, Box 289, Addenbrooke's Hospital, Cambridge, CB2 0QQ, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom.
Abstract
Adipose tissue and the liver play a significant role in the regulation of whole body energy homeostasis, but they have not evolved to cope with the continuous, chronic, nutrient surplus seen in obesity. In this review, we detail how prolonged metabolic stress leads to adipose tissue dysfunction, inflammation and adipokine release that results in increased lipid flux to the liver. Overall, the upshot of hepatic fat accumulation alongside an insulin resistant state, is that hepatic lipid enzymatic pathways are modulated and overwhelmed, resulting in the selective build-up of toxic lipid species, which worsens the pro-inflammatory and pro-fibrotic shift observed in NASH.