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Department of

Pathology and Laboratory Medicine

Photo of  Philip Howles, PhD

Philip Howles, PhD

Associate Professor

Research/Clinical Interests

Research in my lab is aimed at understanding the processes of lipid absorption and metabolism. These studies are especially relevant because of the rapid increase in obesity in developed countries and the consequent rise in Type II diabetes. In addition, hyperlipidemia is a major risk factor for cardiovascular diseases which remain a major couse of morbidity and mortality in "Western" cultures. One project is focused on elucidating the intracellular steps and cellular machinery that are involved in lipid absorption and chylomicron production by the intestinal epithelium. The second project is focused on the selective uptake of cholesterol esters from HDL by hepatocytes and the subsequent processing of that cholesterol for bile acid synthesis, lipoprotein production or secretion as biliary cholesterol. Both projects utilize knockout mice in which the gene for carboxyl ester lipase (CEL, cholesterol esterase, bile salt stimulated lipase) has been ablated. During active lipid absorption, these mice produce intestinal lipoproteins that are dramaticlly different in size and protein composition, suggesting that enzyme plays an important role in chylomicron synthesis and/or secretion - most likely by affecting Golgi function. Absence of a functional CEL gene also appears to alter the processing of HDL-cholesterol by hepatocytes, resulting in changes in bile acid production and biliary cholesterol secretion. All studies involve a combination of physiological, biochemical, and molecular techniques as well as both in vivo and in vitro (cell culture) systems.

Contact Information

Peer Reviewed Publications

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Grayson, Bernadette E; Gutierrez-Aguilar, Ruth; Sorrell, Joyce E; Matter, Emily K; Adams, Michelle R; Howles, Philip; Karns, Rebekah; Seeley, Randy J; Sandoval, Darleen A 2017. Bariatric surgery emphasizes biological sex differences in rodent hepatic lipid handling. Biology of sex differences, 8 , 4

Li, Xiaoming; Wang, Fei; Xu, Min; Howles, Philip; Tso, Patrick 2017. ApoA-IV improves insulin sensitivity and glucose uptake in mouse adipocytes via PI3K-Akt Signaling. Scientific reports, 7 , 41289

Sato, Hirokazu; Zhang, Linda S; Martinez, Kristina; Chang, Eugene B; Yang, Qing; Wang, Fei; Howles, Philip N; Hokari, Ryota; Miura, Soichiro; Tso, Patrick 2016. Antibiotics Suppress Activation of Intestinal Mucosal Mast Cells and Reduce Dietary Lipid Absorption in Sprague-Dawley Rats. Gastroenterology, 151 5, 923-932

Wang, Fei; Kohan, Alison B; Lo, Chun-Min; Liu, Min; Howles, Philip; Tso, Patrick 2015. Apolipoprotein A-IV: a protein intimately involved in metabolism. Journal of lipid research, 56 8, 1403-18

Zhang, Linda S; Sato, Hirokazu; Yang, Qing; Ryan, Robert O; Wang, David Q-H; Howles, Philip N; Tso, Patrick 2015. Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats. American journal of physiology. Gastrointestinal and liver physiology, 309 11, G918-25

Zhang, Linda S; Xu, Min; Yang, Qing; Lou, Danwen; Howles, Philip N; Tso, Patrick 2015. ABCG5/G8 deficiency in mice reduces dietary triacylglycerol and cholesterol transport into the lymph. Lipids, 50 4, 371-9

Zhang, Linda S; Xu, Min; Yang, Qing; Ryan, Robert O; Howles, Philip; Tso, Patrick 2015. Apolipoprotein A-V deficiency enhances chylomicron production in lymph fistula mice. American journal of physiology. Gastrointestinal and liver physiology, 308 7, G634-42

Shen, Ling; Xiong, Ye; Wang, David Q-H; Howles, Philip; Basford, Joshua E; Wang, Jiang; Xiong, Yu Qing; Hui, David Y; Woods, Stephen C; Liu, Min 2013. Ginsenoside Rb1 reduces fatty liver by activating AMP-activated protein kinase in obese rats. Journal of lipid research, 54 5, 1430-8

Howles, Philip N; Hui, David Y 2012. Physiological role of hepatic NPC1L1 in human cholesterol and lipoprotein metabolism: new perspectives and open questions. Journal of lipid research, 53 11, 2253-5

Kohan, Alison B; Howles, Philip N; Tso, Patrick 2012. Methods for studying rodent intestinal lipoprotein production and metabolism. Current protocols in mouse biology, 2 , 219-230

Basford, Joshua E; Wancata, Lauren; Hofmann, Susanna M; Silva, R A Gangani D; Davidson, W Sean; Howles, Philip N; Hui, David Y 2011. Hepatic Deficiency of Low Density Lipoprotein Receptor-related Protein-1 Reduces High Density Lipoprotein Secretion and Plasma Levels in Mice The Journal of biological chemistry, 286 15, 13079-87

Camarota, Lisa M; Woollett, Laura A; Howles, Philip N 2011. Reverse cholesterol transport is elevated in carboxyl ester lipase-knockout mice The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 25 4, 1370-7

Yang, Li; Li, Xiaoming; Ji, Yong; Kohan, Alison B; Wang, David Q-H; Howles, Philip N; Hui, David Y; Lai, Jianghua; Tso, Patrick 2010. Effect of ezetimibe on incretin secretion in response to the intestinal absorption of a mixed meal American journal of physiology. Gastrointestinal and liver physiology, 299 5, G1003-11

Hui, D., E. Labonte and P. Howles 2008. Development and Physiological Regulation of Intestinal Lipid Absorption. III. Intestinal Transporters and Cholesterol Absorption American Journal of Physiology – Gastrointestinal and Liver Physiology , 294 , G839-843

Hui, David Y; Labonté, Eric D; Howles, Philip N 2008. Development and physiological regulation of intestinal lipid absorption. III. Intestinal transporters and cholesterol absorption American journal of physiology. Gastrointestinal and liver physiology, 294 4, G839-43

Labonté, Eric D; Camarota, Lisa M; Rojas, Juan C; Jandacek, Ronald J; Gilham, Dean E; Davies, Joanna P; Ioannou, Yiannis A; Tso, Patrick; Hui, David Y; Howles, Philip N 2008. Reduced absorption of saturated fatty acids and resistance to diet-induced obesity and diabetes by ezetimibe-treated and Npc1l1-/- mice American journal of physiology. Gastrointestinal and liver physiology, 295 4, G776-83

Gilham, Dean; Labonté, Eric D; Rojas, Juan C; Jandacek, Ronald J; Howles, Philip N; Hui, David Y 2007. Carboxyl ester lipase deficiency exacerbates dietary lipid absorption abnormalities and resistance to diet-induced obesity in pancreatic triglyceride lipase knockout mice The Journal of biological chemistry, 282 34, 24642-9

Gilham,D., E. Labonte, J. Rojas, R. Jandacek, P. Howles and D. Hui 2007. Carboxyl ester lipase deficiency exacerbates dietary lipid absorption abnormalities and resistance to diet-induced obesity in pancreatic triglyceride lipase knockout mice Journal of Biological Chemistry , 282 , 24642-24649

Labonté, Eric D; Howles, Philip N; Granholm, Norman A; Rojas, Juan C; Davies, Joanna P; Ioannou, Yiannis A; Hui, David Y 2007. Class B type I scavenger receptor is responsible for the high affinity cholesterol binding activity of intestinal brush border membrane vesicles Biochimica et biophysica acta, 1771 9, 1132-9

Nogueiras, R., P. Wiedmer, D. Perez-Tilve, C. Veyrat-durebex, J. Keogh, G. Sutton, P. Pfluger, T. Castaneda, S. Neschen, S. Hofmann, P. Howles, D. Morgan, S. Benoit, I. Szanto, B. Schrott, A. Schurmann, H. Joost, C. Hammond, D. Hui, S. Woods, K. Rahmouni, A. Butler, I. Farooqi, S. O’Rahilly, F. Rohner-Jeanrenaud and M. Tschop 2007. The central melanocortin system directly controls peripheral lipid metabolism Journal of Clinical Investigation , 117 , 3475-88

Nogueiras, Ruben; Wiedmer, Petra; Perez-Tilve, Diego; Veyrat-Durebex, Christelle; Keogh, Julia M; Sutton, Gregory M; Pfluger, Paul T; Castaneda, Tamara R; Neschen, Susanne; Hofmann, Susanna M; Howles, Philip N; Morgan, Donald A; Benoit, Stephen C; Szanto, Ildiko; Schrott, Brigitte; Schürmann, Annette; Joost, Hans-Georg; Hammond, Craig; Hui, David Y; Woods, Stephen C; Rahmouni, Kamal; Butler, Andrew A; Farooqi, I Sadaf; O 2007. The central melanocortin system directly controls peripheral lipid metabolism The Journal of clinical investigation, 117 11, 3475-88

Hui, David Y; Howles, Philip N 2005. Molecular mechanisms of cholesterol absorption and transport in the intestine Seminars in cell & developmental biology, 16 2, 183-92

Camarota, Lisa M; Chapman, Jamie M; Hui, David Y; Howles, Philip N 2004. Carboxyl ester lipase cofractionates with scavenger receptor BI in hepatocyte lipid rafts and enhances selective uptake and hydrolysis of cholesteryl esters from HDL3 The Journal of biological chemistry, 279 26, 27599-606

Kirby, R Jason; Howles, Philip N; Hui, David Y 2004. Rate of gastric emptying influences dietary cholesterol absorption efficiency in selected inbred strains of mice Journal of lipid research, 45 1, 89-98

Huggins, Kevin W; Camarota, Lisa M; Howles, Philip N; Hui, David Y 2003. Pancreatic triglyceride lipase deficiency minimally affects dietary fat absorption but dramatically decreases dietary cholesterol absorption in mice. The Journal of biological chemistry, 278 44, 42899-905

Hui, David Y; Howles, Philip N 2002. Carboxyl ester lipase: structure-function relationship and physiological role in lipoprotein metabolism and atherosclerosis. Journal of lipid research, 43 12, 2017-30

Kirby, R Jason; Zheng, Shuqin; Tso, Patrick; Howles, Philip N; Hui, David Y 2002. Bile salt-stimulated carboxyl ester lipase influences lipoprotein assembly and secretion in intestine: a process mediated via ceramide hydrolysis. The Journal of biological chemistry, 277 6, 4104-9

Cai, S F; Kirby, R J; Howles, P N; Hui, D Y 2001. Differentiation-dependent expression and localization of the class B type I scavenger receptor in intestine. Journal of lipid research, 42 6, 902-9

Shen, H; Howles, P; Tso, P 2001. From interaction of lipidic vehicles with intestinal epithelial cell membranes to the formation and secretion of chylomicrons. Advanced drug delivery reviews, 50 Suppl 1 , S103-25

Howles, P N; Stemmerman, G N; Fenoglio-Preiser, C M; Hui, D Y 1999. Carboxyl ester lipase activity in milk prevents fat-derived intestinal injury in neonatal mice. The American journal of physiology, 277 3 Pt 1, G653-61

Carter, C P; Howles, P N; Hui, D Y 1997. Genetic variation in cholesterol absorption efficiency among inbred strains of mice. The Journal of nutrition, 127 7, 1344-8

Howles, P N; Carter, C P; Hui, D Y 1996. Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice. The Journal of biological chemistry, 271 12, 7196-202