9.2. 2022, Laboratory of Adipose Tissue Biology

Laboratory name: Adipose Tissue Biology

Supervisor: Martin Rossmeisl, MD, Ph.D. (martin.rossmeisl@fgu.cas.cz)

PhD project: The role of impaired autophagy in NAFLD development and its restoration to improve the efficacy of n-3 fatty acids

Obesity is associated with non-alcoholic fatty liver disease (NAFLD), which represents a spectrum of conditions ranging from increased intrahepatic accumulation of triacylglycerols (hepatic steatosis) to non-alcoholic steatohepatitis (NASH) characterized by hepatocellular inflammation that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. The mechanisms involved in the transition from benign steatosis to the more clinically severe stages of NAFLD are not fully understood. The severity of NAFLD may be related to autophagy failure leading to accumulation of dysfunctional peroxisomes associated with induction of oxidative tissue damage. Dietary n-3 fatty acid (omega-3) supplementation may modulate lipid metabolism, thereby reducing hepatic steatosis, but its efficacy on more advanced stages of NAFLD (e.g. NASH) is low.

The aim of this PhD project is to characterize the role of impaired autophagy in NAFLD progression, the effects of omega-3 supplementation on different stages of NAFLD, and the potential benefits of combined treatment with autophagy inducers and omega-3. The selected PhD student will conduct dietary intervention studies using several chemical forms of omega-3 in a mouse model of advanced obesity-related NAFLD. This will include phenotyping of glucose metabolism and insulin resistance in vivo (tolerance assays, hyperinsulinemic-euglycemic clamp), ex vivo functional analyses in isolated hepatocytes, as well as biochemical, histological, and molecular biological techniques. 

Candidate’s profile (requirements):

We are seeking outstanding self-motivated candidates with master's degree or equivalent in physiology, biochemistry, molecular biology, medicine or related fields, or those expecting to obtain their degree this year. Candidates should be fluent in English. This position involves extensive work with laboratory animals (primarily mice). Experience with animal models (mouse, rat), in vivo phenotyping techniques, in vitro cell cultures and/or molecular biology techniques is advantage.

References:

• Mitrovic M. et al., Omega-3 phospholipids and obesity-associated NAFLD: Potential mechanisms and therapeutic perspectives. Eur J Clin Invest. 2021 Jul 22;e13650.
• Sistilli G. et al., Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity. Nutrients. 2021 Jan 29;13(2):437.
• Rossmeisl M. et al., Increased plasma levels of palmitoleic acid may contribute to beneficial effects of Krill oil on glucose homeostasis in dietary obese mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Aug;1865(8):158732.