Molecular Metabolism

About the group

Nutrition, physical activity, genes and gender are environmental factors important for the development of metabolic diseases such as fatty liver, insulin resistance and obesity.

The molecular metabolism group study how genes and lipids regulate diet induced metabolic diseases. We also study the molecular mechanisms behind how physical activity can protect against the development of metabolic diseases.  Finally, we study why the genetic regulation of a variety of metabolic disease varies between the sexes.

An increasing number of people develop metabolic diseases. Eating an unhealthy diet, sedentary lifestyle, genetic variations, sex and age are all factors known to play important roles in the development of metabolic diseases. We want to develop new strategies to combat metabolic diseases. These strategies encompass both prevention and therapy. We are currently focusing on understanding how non-alcoholic fatty liver develop into fibrotic non-alcoholic steatohepatitis (NASH). We want to identify and molecularly clarify how specific genes and hepatic lipid species contribute to development of NASH. New knowledge about why and how some, but not all, people 

Projects

• The effect of genes and lipids in the development of non-alcoholic steatohepatitis
• Sex differences in adipose tissue metabolism
• Physical activity and insulin resistance

Cooperation

• Professor Aldons Jake Lusis, Department of Medicine, Division of Cardiology, UCLA, USA
• Professor Andrea Hevener, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, UCLA, USA
• Associate Professor Knut T. Dalen, Department of Nutrition, Division of Molecular Nutrition, IMB, Faculty of Medicine, University of Oslo, Norway
• Professor Kåre I. Birkeland, Oslo University Hospital, Oslo, Norway.
• Professor Truls Raastad, The Norwegian School of Sport Sciences, Oslo, Norway
• Professor Gunnar Pejler, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden.
• Assistant Professor Karthickeyan Chella Krishnan, Pharmacology & Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, US

Selected Publications

1. Norheim F, Chella Krishnan K, Bjellaas T, Vergnes L, Pan C, Parks BW , Meng Y, Lang J, Ward JA, Reue K, Mehrabian M, Gundersen TE, Péterfy M, Dalen KT, Drevon CA, Hui ST, Lusis AJ, Seldin MS: Regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis. Molecular Systems Biology, 2021 Jan;17(1):e9684.
2. Maak S, Norheim F, Drevon CA, Erickson HP: Progress and challenges in the biology of FNDC5 and irisin. Endocr Rev. 2021 Jul 16;42(4):436-456.
3. Norheim F, Hasin-Brumshtein Y, Vergnes L, Seldin MM, Chella Krishnan K, Pan C, Hui ST, Mehrabian M, Zhou Z, Gupta S, Parks BW, Walch A, Reue K, Hofmann SM, Arnold AP, and Lusis AJ: Gene-by-sex interactions in mitochondrial functions and cardio-metabolic traits. Cell Metabolism. 2019 Apr 2;29(4):932-949.e4.
4. Hui ST, Kurt Z, Tuominen L, Norheim F, Davis RC, Pan C, Dirks DL, Magyar C, Canizales-Quinteros S, Yang X, Beaven SW, Huertas-Vazquez A, Lusis AJ: The Genetic Architecture of Diet-induced Hepatic Fibrosis in mice with a Humanized Lipoprotein Profile. Hepatology. 2018 Dec;68(6):2182-2196. doi: 10.1002/hep.30113. Epub 2018 Nov 8.
5. Norheim F, Bjellaas T, Hui ST, Chella Krishnan K, Lee J, Gupta S, Pan C, Hasin-Brumshtein Y, Parks BW, Li DY, Bui HH, Mosier M, Wu Y, Hazen SL, Gundersen TE, Mehrabian M, Tang WHW, Hevener AL, Drevon CA, Lusis AJ: Genetic and sex specific regulation of hepatic ceramide levels and insulin resistance. J Lipid Res. 2018 Jul;59(7):1164-1174.
6. Norheim F, Hui ST, Kulahcioglu E, Mehrabian M, Cantor RM, Pan C, Parks BW, Lusis AJ: Genetic and hormonal control of hepatic steatosis in female and male mice. J Lipid Res. 2017 Jan;58(1):178-187.
7. Chella Krishnan K, Kurt Z, Barrere-Cain R, Sabir S, Das A, Floyd R, Vergnes L, Zhao Y, Che N, Charugundla S, Qi H, Zhou Z, Meng Y, Pan C, Seldin MM, Norheim F, Hui ST, Reue K, Lusis AJ, and Yang X: Integration of Multi-omics Data from The Hybrid Mouse Diversity Panel Predicts Novel Mechanisms Underlying Non-Alcoholic Fatty Liver Disease. Cell Systems. 2018 Jan 24;6(1):103-115.e7.
8. Parks BW, Nam E, Org E, Kostem E, Norheim F, Hui ST, Pan C, Civelek M, Rau CD, Bennett BJ, He A, Castellani LW, Knight R, Drake TA, Drevon CA, Zinker B, Kirby M, Gargalovic P, Kirchgessner T, Eskin E, Lusis AJ: Genetic Control of Obesity in Response to a High-Fat, High-Sucrose Diet; A Systems Genetics Analysis in the Mouse. Cell Metabolism. 2013, Jan 8;17(1); 141-152
9. Sindre Lee, Frode Norheim, Hanne L. Gulseth, Kåre I. Birkeland, Christian A. Drevon: Effects of three months exercise on plasma adipokines levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary men with and without dysglycemia. Diabetologia. 2019 Jun;62(6):1048-1064. doi: 10.1007/s00125-019-4866-5. Epub 2019 Apr 22.
10. Hjorth M, Langleite TM, Lee S, Holen T, Gulseth HL, Kielland A, Birkeland KI, Jensen J, Drevon CA, Norheim F: Myostatin in relation to physical activity and pre-diabetes. Acta Physiol (Oxf). 2016 May;217(1):45-60. doi: 10.1111/apha.12631.