Nonalcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from fatty liver to non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. It is evident that one of the central features of NAFLD and NASH is the lack of capacity of the liver to handle the primary metabolic energy substrates, carbohydrates, and fatty acids, leading to accumulation of toxic lipid species. Thus, clarifying the sources and fates of fatty acids in hepatocytes is essential for understanding the metabolic foundations of NAFLD and NASH. Our work aims to obtain an understanding of the role of enzymes in the regulation of lipid homeostasis, especially in the liver. Among other key enzymes, we expect that Hydroxysteroid 17beta dehydrogenase enzymes present with a central role in the cholesterol and lipid metabolism and metabolic homeostasis, and thus, are involved in pathogenesis of NAFLD and NASH. They can also be pharmacologically inhibited, and thus form novel candidates for the treatment of liver diseases associated with fat accumulation.
PIs: Leena Strauss, PhD, adjunct professor; Matti Poutanen, PhD, professor
Members involved
Postdoctoral Researchers: Guillermo Martinez-Nieto, PhD.
Doctoral candidates: Hanna Heikelä, MSc; Laura Mairinoja, MSc.
Selected publications about research
Gjorgjieva M, Sobolewski C, Ay AS, Abegg D, Correia de Sousa M, Portius D, Berthou F, Fournier M, Maeder C, Rantakari P, Zhang FP, Poutanen M, Picard D, Montet X, Nef S, Adibekian A, Foti M. Genetic Ablation of MiR-22 Fosters Diet-Induced Obesity and NAFLD Development. J Pers Med. 2020 Oct 14;10(4):170
Heikelä H, Ruohonen ST, Adam M, Viitanen R, Liljenbäck H, Eskola O, Gabriel M, Mairinoja L, Pessia A, Velagapudi V, Roivainen A, Zhang FP, Strauss L, Poutanen M. Hydroxysteroid (17β) dehydrogenase 12 is essential for metabolic homeostasis in adult mice. Am J Physiol Endocrinol Metab. 2020 Sep 1;319(3):E494-E508.
Colldén H, Landin A, Wallenius V, Elebring E, Fändriks L, Nilsson ME, Ryberg H, Poutanen M, Sjögren K, Vandenput L, Ohlsson C. The gut microbiota is a major regulator of androgen metabolism in intestinal contents. Am J Physiol Endocrinol Metab. 2019 Dec 1;317(6):E1182-E1192.
Adam M, Heikelä H, Sobolewski C, Portius D, Mäki-Jouppila J, Mehmood A, Adhikari P, Esposito I, Elo LL, Zhang FP, Ruohonen ST, Strauss L, Foti M, Poutanen M.Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice. FASEB J. 2018 Jun;32(6):3434-3447.
Ohlsson C, Hammarstedt A, Vandenput L, Saarinen N, Ryberg H, Windahl SH, Farman HH, Jansson JO, Movérare-Skrtic S, Smith U, Zhang FP, Poutanen M, Hedjazifar S, Sjögren K. Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice. Am J Physiol Endocrinol Metab. 2017 Oct 1;313(4):E450-E462.