Philip N. Howles, PhD

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. 

- Research Assistant Professor, Department of Pathology and Laboratory Medicine, Metabolic Disease Institute Cincinnati - GRIA 252

Grant: #R01 HL078900 Investigators:Howles, Philip 08-01-2006 -07-31-2012 National Heart, Lung and Blood Institute Carboxyl ester lipase affects hepatic HDL metabolism Role:PI $1,597,449.00 Active Level:Federal

Investigators:Howles, Philip 08-01-2002 -07-31-2005 Department of Agriculture Pancreatic Carboxyl Ester Lipase Influences Chylomicron Production and Metabolism Role:PI $275,000.00 Closed Level:Federal

Grant: #5-R29-HD-33926-05-A0-S0-E0 Investigators:Howles, Philip 08-03-1995 -07-31-2001 National Institute of Child Health and Human Development Lipid and Cholesterol Esterase in Neonatal Gut Integrity Role:PI $529,434.00 Closed Level:Federal

Grant: #SW-97-16-B-02-A0-S0-E0 Investigators:Howles, Philip 07-01-1997 -06-30-2000 American Heart Association - Southwest Chapter Transcytosis and Vascular Tone in Caveolin-1 Deficient Mice Role:PI $60,000.00 Closed Level:Private Non-Profit

Grant: #R01 DK076907 Investigators:Howles, Philip; Hui, David 08-01-2007 -07-31-2012 National Inst of Diabetes and Digestive and Kidney Disease Physiological Role of NPC1L1 in Lipid Transport and Metabolism Role:Collaborator $1,256,878.00 Closed Level:Federal

Grant: #R01 DK076928 Investigators:Howles, Philip; Hui, David; Tso, Patrick P.W. 08-01-2007 -07-31-2013 National Inst of Diabetes and Digestive and Kidney Disease Functional and Molecular Study of Intestinal Cholesterol Transporters and Absorption Role:Collaborator $1,564,045.00 Active Level:Federal

Grant: #07-MCG-20 Investigators:Howles, Philip 11-01-2007 -06-30-2009 National Inst of Diabetes and Digestive and Kidney Disease Lymph Fistula Mouse: A Novel Model for Studying Incretin Secretion Role:PI $60,000.00 Closed Level:Federal

Grant: #1 R01 DK077170-01A2 Investigators:Howles, Philip; Hui, David; Tso, Patrick P.W. 09-30-2009 -05-31-2013 National Inst of Diabetes and Digestive and Kidney Disease Role of NPC1L1 in Regulating Energy Metabolism, Nutrient Utilization and Weight Gain Role:PI $719,514.00 Active Level:Federal

Grant: #U24 DK059630 Investigators:Benoit, Stephen; Dalessio, David; Davidson, William; Howles, Philip; Hui, David; Jandacek, Ronald; Obici, Silvana; Schultz, Jo El; Seeley, Randy; Tschoep, Matthias; Tso, Patrick P.W.; Welge, Jeffrey; Woods, Stephen; Woollett, Laura 09-16-2011 -06-30-2016 National Inst of Diabetes and Digestive and Kidney Disease Cincinnati Mouse Metabolic Phenotyping Center Role:Collaborator $1,619,789.00 Active Level:Federal

Grant: #R01 DK103557 Investigators:Howles, Philip; Tso, Patrick P.W. 04-01-2015 -03-31-2020 National Inst of Diabetes and Digestive and Kidney Disease Apolipoprotein AV and intestinal transport Role:Collaborator $379,161.00 Awarded Level:Federal

Grant: #U2CDK059630 Investigators:Benoit, Stephen; Davidson, William; Howles, Philip; Liu, Min; Reyes, Teresa; Tso, Patrick P.W.; Ulrich-Lai, Yvonne; Welge, Jeffrey; Woods, Stephen; Woollett, Laura 08-01-2016 -06-30-2021 National Inst of Diabetes and Digestive and Kidney Disease Cincinnati Mouse Metabolic Phenotyping Center Role:Collaborator $926,069.68 Active Level:Federal

Peer Reviewed Publications

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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

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

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

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

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

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

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

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 More Information

Lipase,Cell Cycle,Dietary Lipid,Newborn Animal,Enzyme Activity,Sterol Esterase,Laboratory Mouse,Lipid Metabolism,Southern Blotting,Nutrition Related Tag,Programmed Cell Death,Polymerase Chain Reaction,Gastrointestinal Epithelium,Congenital Gastrointestinal Disorder,Gastrointestinal Nutrient Absorption

Research - Metabolic Diseases Institute
2120 Galbraith Road
Reading  Ohio, 45215
Phone: (513) 558-4288
philip.howles@uc.edu