Fatty acids are important signalling molecules that regulate a wide-range of functions within the body, such as insulin sensitivity, inflammation, and metabolism. My research program is focused on better understanding the biological activities of individual fatty acids, and how their activity is regulated by fatty acid desaturases.
Stearoyl-coenzyme A (SCD) is rate limiting for the conversion of saturated fatty acids into monounsaturated fatty acids. Previous work in the field has shown that reduced SCD activity is associated with a resistance to diet-induced obesity, while increased SCD activity is positively correlated with body weight. Our lab has shown that SCD has broad implications on adipose tissue lipid handling by regulating triacylglycerol biosynthesis, fatty acid re-esterification, and lipolysis. Moreover, we have shown the relationship between SCD and markers of whole-body inflammation in humans is influenced by genetic variation. Building on these previous findings, my lab is currently investigating how changes in SCD activity influence adipose tissue function in different depots (e.g., subcutaneous vs. visceral), and whether the outcomes related to reduced SCD activity can be circumvented with dietary fats.
Fatty acid desaturase 1 and 2 (FADS1 and FADS2) are critical in the conversion of the essential omega-3 dietary fat (alpha-linolenic acid, ALA) into longer chain polyunsaturated fats, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To date, it has been challenging to define the independent roles of these individual omega-3 fats due to the continuous, albeit low, conversion of ALA into EPA and DHA. EPA and DHA are known to have strong anti-inflammatory activity and serve as the precursors for inflammation resolving metabolites. In contrast, the role of ALA is far less characterized. ALA is highly consumed in the diet; however, the typical Western diet is often characterized as being deficient in EPA and DHA. This means that most individuals derive EPA and DHA from the endogenous conversion of ALA. We (and others) have shown that the conversion in humans is highly influenced by variation in the FADS1 and FADS2 genes. This has led to classifying people as either a “low converter” or a “high converter”. Interestingly, we have recently shown that “low converters” also have higher whole-body fat oxidation compared to “high converters”. This suggests that FADS1 and FADS2 may have broader implications on whole-body energy metabolism than previously recognized. Using knockout mice and cell culture techniques, my lab is currently investigating the independent roles of individual omega-3 fats on the regulation of whole-body metabolism, and how these roles are influenced by FADS 1 and FADS2. In conjunction with these basic studies, my lab is also conducting human clinical trials to examine how genetic variation in FADS may influence these various endpoints and whether this gene can be used for personalized nutrition.
Dragos SM, Bergeron KF, Desmarais F, Suitor K, Wright DC, Mounier C, Mutch DM. 2017. Reduced SCD1 activity alters markers of fatty acid re-esterification, glyceroneogenesis, and lipolysis in murine white adipose tissue and 3T3-L1 adipocytes. Am J Physiol Cell Physiol; 313 (3): C295-304.
Badoud F, Brewer D, Charchoglyan A, Cuthbertson DJ, Mutch DM. 2017. Multi-omics integrative investigation of fatty acid metabolism in obese and lean subcutaneous tissue. OMICS; 21 (7): 371-79.
Roke K, Walton K, Klingel SL, Harnett A, Subedi S, Haines J, Mutch DM. 2017. Evaluating changes in omega-3 fatty acid intake after receiving personal FADS1 genetic information: a randomized nutrigenetic intervention. Nutrients; 9 (3): E240.
Zulyniak MA, Roke K, Gerling C, Logan SL, Spriet LL, Mutch DM. 2016. Fish oil regulates blood fatty acid composition and oxylipin levels in healthy humans: a comparison of young and older men. Mol Nutr Food Res; 60 (3): 631-41.
Ralston JC, Metherel AH, Stark KD, Mutch DM. 2016. SCD1 mediates the influence of exogenous saturated and monounsaturated fatty acids in adipocytes: Effects on cellular stress, inflammatory markers and fatty acid elongation. J Nutr Biochem; 27: 241-8.
Ralston JC, Matravadia S, Gaudio N, Holloway GP, Mutch DM. 2015. Polyunsaturated fatty acid regulation of adipocyte FADS1 and FADS2 expression and function. Obesity (Silver Spring); 23 (4): 725-8.
Badoud F, Perreault M, Zulyniak MA, Mutch DM. 2015. Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals. FASEB J; 29 (3): 748-58.
Roke K, Mutch DM. 2014. The role of FADS1/2 polymorphisms on cardiometabolic markers and fatty acid profiles in young adults consuming fish oil supplements. Nutrients; 6 (6): 2290-304.
Perreault M, Roke K, Badawi A, Nielsen DE, Abdelmagid SA, El-Sohemy A, Ma DW, Mutch DM. 2014. Plasma levels of 14:0, 16:0, 16:1n-7, and 20:3n-6 are positively associated, but 18:0 and 18:2n-6 are inversely associated with markers of inflammation in young healthy adults. Lipids; 49 (3): 255-63.
Roke K, Ralston JC, Abdelmagid S, Nielsen DE, Badawi A, El-Sohemy A, Ma DW, Mutch DM. 2013. Variation in the FADS1/2 gene cluster alters plasma n-6 PUFA and is weakly associated with hsCRP levels in healthy young adults. Prostaglandins Leukot Essent Fatty Acids; 89 (4): 257-63.
Shaw B, Lambert S, Wong MH, Ralston JC, Stryjecki C, Mutch DM. 2013. Individual saturated and monounsaturated fatty acids trigger distinct transcriptional networks in differentiated 3T3-L1 preadipocytes. J Nutrigenet Nutrigenomics; 6 (1): 1-15.
Stryjecki C, Roke K, Clarke S, Nielsen D, Badawi A, El-Sohemy A, Ma DW, Mutch DM. 2012. Enzymatic activity and genetic variation in SCD1 modulate the relationship between fatty acids and inflammation. Mol Genet Metab; 105 (3): 421-7.
Stryjecki C, Mutch DM. 2011. Dietary fatty acids, adipokines, and obesity. Eur J Clin Nutr; 65 (3): 285-97.
Merino DM, Johnston H, Clarke S, Roke K, Nielsen D, Badawi A, El-Sohemy A, Ma DW, Mutch DM. 2011. Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults. Mol Genet Metab; 103 (2): 171-8.
Mutch DM, Wahli W, Williamson G. 2005. Nutrigenomics and Nutrigenetics: The emerging faces of nutrition. The FASEB J; 19: 1602-1616.