Rene Jacobs

Rene JacobsRené Jacobs, PhD

Office:     4-002 Li Ka Shing Centre for Health Research Innovation
Mail:        University of Alberta, Edmonton, AB Canada T6G 2E1
Phone:    780-492-2343 (Office)
              780-492-7561 (Lab)
Fax:        780-492-9270
Email:     rjacobs@ualberta.ca

 

 

 


 

Current Position

 

Assistant Professor, Department of Agricultural, Food & Nurtitional Science

 

Research Area

 

Nutrition and metabolism

 

Research Goals

 

Dr. Jacobs’ research program incorporates “state of the science” in vivo techniques, biochemical analysis and nutrigenomics as part of a comprehensive, multidisciplinary approach seeking to understand the complex interactions involved in the etiology of obesity, Type 2 diabetes and other chronic diseases.

 

Current Research Activities

 

A. Investigate the role of micronutrients (folate, cobolamin and choline) in the development of obesity and insulin resistance. [2010-2014]

 

B. Determine the importance of phosphatidylcholine biosynthesis in lipoprotein production and atherosclerosis development. [2012-2015]

 

C. Investigate the efficacy of creatine in treating non-alcoholic fatty liver disease [2012-2015]

 

D. Study the role of the vagus nerve in regulating hepatic lipid metabolism and whole-body energy metabolism. [2011-2013]

 

Human Studies

 

Title: Estimation of current choline intake in Albertan woman during pregnancy and lactation (non-intervention)

Synopsis: In collaboration with Dr. Catherine Field, Dr. Jonathon Curtis and the APRON team, we are interested in estimating choline intake in over 2000 woman during pregnancy to examine links to infant health and development [In progress]

 

Other Activities and Affiliations

 

2011-2013       Committee Member- CIHR Doctoral Research Awards (DRA) and Canada Graduate Scholarships Master's Awards (CGA)

2010-2012       Co-organizer and host of the 2012 Canadian Lipoprotein Conference

 

Biography

 

University of Alberta

 

 

Assistant Professor

 

2009- Present         

 

 

Dept. of Agricultural, Food and Nutritional Sciences

 

University of Alberta

Research Associate

2007-2008

Dept. of Biochemistry

University of Alberta

Postdoc.

2002-2007

Molecular and Cell Biology of Lipids and Dept. of Biochemistry

Memorial University of Newfoundland

Ph.D.

1996-2002

Dept. of Biochemistry

Memorial University of Newfoundland

B.Sc. (Hon)

1992-1996

Dept. of Biochemistry

 

Major Achievements

 

1. Homocysteine Metabolism in Type 1 Diabetes Mellitus- Studies conducted during my PhD elucidated the biochemical and molecular mechanisms explaining why plasma homocysteine levels are decreased in the Type 1 diabetic rats. These findings were significant because they were the first to explain the observations found in humans. Subsequent studies determined that homocysteine metabolism is tightly regulated by several hormones (insulin, glucagon, glucocorticoids, and thyroid). The data from these studies were presented in 12 conferences and resulted in 5 peer-reviewed publications. As part of collaboration, I have continued to work on the regulation of homocysteine and phospholipid metabolism in Type 2 diabetes rats. One manuscript has been submitted for this project.

2. Altered Hepatic Lipid Metabolism Influences Plasma Lipoprotein Levels- As part of my post-doctoral training, I investigated how the liver modulates circulating lipoproteins in genetically-modified mice. With the assistance of our collaborators in Columbia University, we developed a liver-specific CTP:phosphocholine cytidylyltransferase-α   knockout mouse (LCTαKO). The LCTαKO had impaired hepatic phosphatidylcholine synthesis which resulted in lower plasma VLDL and HDL levels. The reduction in plasma lipoprotein levels were reversed when we administered an adenovirus containing the CTα cDNA. In fact, the levels of HDL and VLDL were directly proportional to hepatic CT activity. These findings are significant because they provide mechanistic evidence linking hepatic phosphatidylcholine synthesis and circulating levels of lipoproteins.

3. Phosphatidylethanolamine N-Methyltransferase and Methylation Demand- Studies conducted during my postdoctoral training were the first to show that physiological regulation of phosphatidylethanolamine N-methyltransferase (PEMT) alters homocysteine metabolism in mice. Our labs’ (Vance and Brosnan) work on this subject resulted in the novel idea that PEMT is an important consumer of methyl groups. This idea was published as a commentary in AJCN and was my first corresponding-author manuscript. We have published 3 other manuscripts on this topic.

4. Hepatic Phosphatidylcholine Biosynthesis and the Metabolic Syndrome- More recently, we attempted to explain why PEMT knockout mice are protected from diet-induced obesity, insulin resistance, and atherosclerosis. The data from these studies are the first to link de novo choline synthesis to altered whole-body energy metabolism. Our data suggests that PEMT is potential pharmaceutical target to treat disorders related to the metabolic syndrome. I have presented this study during 5 conferences. We have published 2 manuscripts (ATVB, JBC, and Obesity) on this subject. 

5. Hepatic Phosphatidylcholine Biosynthesis and Liver Function- Finally, we have investigated the relationship between PC biosynthesis and liver function. When fed a high fat diet for 1 week, the LCTαKO have normal weight gain; however, they develop severe liver disease (non-alcoholic steatohepatitis). The cause of this disease is unclear, but appears to be linked to a combination of lower hepatic PC and higher hepatic ceramide and diacylglyerol levels (BBA 2011). In a related study, we provided evidence that the hepatic ratio of phosphatidylcholine to phosphatidylethanolamine predicts survival after partial hepatectomy in mice (Hepatology 2011, CJPP 2012). Finally, a collaborative project with a lab at Harvard University has identified PC as a novel regulator of SREBP-1. We show that by blocking PC synthesis in C. elegans, mouse liver and human cells causes elevated SREBP-1-dependent transcription and also lipid droplet accumulation. We suggest that nutritional, genetic or environmental limiting PC production may activate SREBP-1, contributing to human metabolic disorders. This study was recently published Cell (November 2011).

 

Selected Publications

 

1.      Ling NJ, Zhu LF, Vance DE, Jacobs RL. Impaired phosphatidylcholine biosynthesis does not attenuate liver regeneration after 70% partial hepatectomy in hepatic CTP:phosphocholinecytidylyltransferase α-deficient mice. Canadian Journal of Physiology and Pharmacology. 2012 (In Press)

2.      Wu G, Zhang L, Li T, Lopaschuk G, Vance DE, Jacobs RL. Choline Deficiency attenuates body weight gain and improves glucose tolerance in ob/ob mice. Journal of Obesity. 2012 Article ID 319172, 7 pages

3.      Ling NJ, Chaba T, Zhu LF, Jacobs RL, Vance DE. Hepatic ratio of phosphatidylcholine to phosphatidylethanolamine predicts survivability after 70% partial hepatectomy in mice. Hepatology. 2012 Apr;55(4):1094-102.

4.      Walker AK, Jacobs RL, Watts JL, Rottiers V, Jiang K, Finnegan DM, Shioda T, Hansen M, Yang F, Niebergall L, Vance DE, Hart AC, Naar AM.  Control of one-carbon genes by SERBP-1 links SAMe production, phosphatidylcholine biosynthesis, and hepatic lipogenesis. CELL. 2011 November 11, 147:1-13

5.      Deminice R, da Silva RP, Lamarre SG, Brown C,   Furey G, McCarter S, Jordao AA, Kelly KB, Jacobs RL, Brosnan ME, Brosnan JT. Creatine supplementation prevents the accumulation of fat in the livers of rats fed a high-fat diet. Journal of Nutrition. 2011 141: 1799-1804

6.      Niebergall LJ, Jacobs RL, Chaba T, Vance DE. Phosphatidylcholine protects against steatosis in mice but not non-alcoholic steatohepatitis. Biochim Biophys Acta. 2011 1811:1177-85

7.      Jacobs RL, Zhao Y, Koonen DP, Sletten T, Su B, Lingrell S, Cao G, Peake DA, Kuo MS, Proctor SD, Kennedy BP, Dyck JR, Vance DE. Impaired de novo choline synthesis explains why phosphatidylethanolamine N-methyltransferase-deficient mice are protected from diet-induced obesity. J Biol Chem. 2010 July; 285(29):22403-22413.Epub 2010 May 7

8.      Koonen DP, Sung MM, Kao CK, Dolinsky VW, Koves TR, Ilkayeva O, Jacobs RL, Vance DE, Light PE, Muoio DM, Febbraio M, Dyck JR. Alterations in Skeletal Muscle Fatty Acid Handling Predisposes Middle-aged Mice to Diet-induced Insulin Resistance. Diabetes. 2010 Jun;59(6):1366-75. Epub 2010 Mar 18

9.      Koonen, DPY, Jacobs RL, Febbraio M, Young ME, Ong H, Vance DE, Dyck JRB. Increased Hepatic CD36 Expression Contributes to Dyslipidemia Associated with Diet-Induced Obesity. Diabetes. 2007; 56: 2863 -2871. Epub 2007 Aug 29.

Stead LM, Brosnan JT, Brosnan ME, Vance DE, Jacobs RL.  Is it time to re-evaluate methyl balance in humans? Am J Clin Nutr. 2006;83(1):5-10.

 

Trainees

 

Grad Students: Karen Kelly, Nusaibah ab Aziz, Erin Lewis (co-supervisor), Bella Gao (co-supervisor)

Postdoctoral Fellows: Robin da Silva, Ala Rajabi, Jean-Claude Bakala (co-supervisor)

 

Websites of interest

 

http://www.mcvd.ualberta.ca/en/Research/ReneJacobs.aspx