Paul S. MacLean, Ph.D.

Assistant Professor of Medicine
Division of Endocrinology, Diabetes, and Metabolism

Contact Information

Office Location: Research Complex 1 North, Rm 5108
Phone #: (303)724-3030
Fax#: (303)724-3031
Email: Paul.MacLean@uchsc.edu

Mailing Address:
University of Colorado Denver
Center for Human Nutrition, F8305
PO Box 6511
Denver, CO 80045

Research Interests

My work Centers on understanding the metabolic adaptations to weight reduction that promote weight regain, with a particular emphasis on the utilization of ingested fuels in the peripheral tissues. We employ obesity-prone rats to model the process of weight regain that occurs in many humans who are trying to lose weight. The particular tools we have at our disposal include indirect calorimetry, dual energy x-ray absorptiometry, and the ingestion of radiolabelled tracers to examine fuel metabolism. We are pursuing adenoviral gene delivery to peripheral tissues to examine the function of specific proteins in fuel metabolism.

Educational/Professional Background

Dr. MacLean joined the UCD faculty in 2001 after receiving his research education and training at Brigham Young and East Carolina Universities. His research efforts are focused on understanding the metabolic contribution to the obesity epidemic. His collaborative efforts with Dr. James Hill (NIH R01 DK038088) have established a rodent paradigm of prolonged weight reduction that he is using to: 1) characterize the metabolic changes that occur with weight loss that promote weight regain; and 2) identify nutritional, environmental, and pharmaceutical therapies to counteract the metabolic drive to regain weight after weight loss. Dr. MacLean is also funded (NIH K01 DK067403) to pursue a more focused examination of the regulation of transcription factors in skeletal muscle and their involvement in promoting lipid accumulation during weight regain. This work is based upon the hypothesis that the sterol response element binding protein (SREBP) family of transcription factors play a critical role in skeletal muscle, liver, and adipose tissue, to promote a high rate of lipid accumulation and weight regain after weight loss. . Dr. MacLean is Associate Director of both the Metabolic Core Laboratory and the Energy Balance Core Laboratory that are affiliated with the Colorado Clinical Nutrition Research Unit (P30 DK48520) and the UCD Center for Human Nutrition.

Recent Publications

• MacLean PS , Bower JF, Vadlamudi S, Green T, Barakat HA. Lipoprotein subpopulation distributions in lean, obese, and type 2 diabetic women: a comparison of African and Caucasian Americans. Obes Res 8:62-70, 2000.
• MacLean PS , Vadlamudi S, MacDonald KG, Pories WJ, Houmard J, Barakat HA. Impact of insulin resistance on lipoprotein subpopulation distribution in lean and obese women. Metabolism 49:285-292, 2000.
• Houmard JA, Cox JH, MacLean PS, Barakat HA. Effect of short-term exercise training on leptin and insulin action. Metabolism 49:858-861, 2000.
• MacLean PS , Barakat HA. Insulin does not regulate the promoter of cholesteryl ester transfer protein (CETP) in HIRc/pCETP-CAT cells. Mol Cell Biochem 211:1-7, 2000.
• MacLean PS , Vadlamudi S, Hao E, Barakat HA. Differential expression of cholesteryl ester transfer protein (CETP) in the liver and plasma of fasted and fed transgenic mice. J Nutri Biochem 11:318-325, 2000.
• MacLean PS , Zheng D, Dohm GL. Muscle glucose transporter (GLUT4) gene expression during exercise. Exerc Sport Sci Rev 28:148-152, 2000.
• MacLean PS , Tanner CJ, Houmard JA, Barakat HA. Plasma cholesteryl ester transfer activity is not linked to insulin sensitivity. Metabolism 50:783-788, 2001.
• Zheng D, MacLean PS, Pohnert SC, Knight JB, Olson AL, Winder WW, Dohm GL. Regulation of muscle GLUT4 transcription by AMP-activated protein kinase. J Appl Physiol 91: 1073-1083, 2001.
• MacLean PS , Zheng D, Jones JP, Olson AL, Dohm GL. Exercise-induced transcription of the muscle glucose transporter (GLUT-4) gene. Biochem Biophys Res Comm 292: 409-414, 2002.
• Muoio DM, MacLean PS, Lang DB, Li S, Houmard JA, Way JM, Winegar DA, Corton JC, Dohm GL, Kraus WE. Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) a knock-out mice. Evidence for compensatory regulation by PPAR d . J Biol Chem 277 (29): 26089-97, 2002.
• Bizeau ME, MacLean PS, Johnson GC, Wei Y. Skeletal muscle SREBP-1c decreases with fasting and increases with feeding in rats. J Nutri 133: 1787-1792, 2003.
• MacLean PS , Bower JF, Vadlamudi S, Osborne JN, Bradfield JF, Burden HW, Bensch WH, Kauffman RF, Barakat HA. Cholesteryl ester transfer protein (CETP) expression prevents diet-induced atherosclerotic lesions in male db/db mice. Arterioscler Thromb Vasc Biol 23:1412-1415, 2003.
• MacLean PS . Cholesteryl ester transfer protein in the metabolic syndrome. International Atherosclerosis Society (http://www.athero.org/commentaries/comm227.pdf, 2003).
• MacLean PS , Higgins JA, Johnson GC, Fleming-Elder BK, Peters JC, Hill JO. Metabolic adjustments with the development, treatment, and recurrence of obesity in obesity-prone rats. Am J Physiol Regul Integr Comp Physiol 287(2):R288-97, 2004.
• MacLean PS , Higgins JA, Johnson GC, Fleming-Elder BK, Donahoo WT, Melanson EL, Hill JO. Enhanced metabolic efficiency contributes to weight regain after weight loss in obesity-prone rats. Am J Physiol Regul Integr Comp Physiol 287:R1306-15, 2004.
• MacLean PS , Vadlamudi S, MacDonald KG, Pories WJ, Barakat HA. Suppression of hepatic CETP expression in obese humans with the development of type 2 diabetes mellitus. J Clin Endo Metab 90, 2250-8, 2005.
• MacLean PS . A peripheral perspective of weight regain. Am J Physiol Regul Integr Comp Physiol 288:1447-9, 2005.
• Qiao L, MacLean PS, Schaack J, Orlicky DJ, Darimont C, Pagliassotti MJ, Friedman JE, Shao J. C/EBP a regulates human adiponectin gene transcription through an intronic enhancer. Diabetes 54(6): 1744-1754, 2005.
• MacLean PS , Jackman M, Bessesen DH. Compensatory Response to Reducing Weight. Drug Discovery Today: Disease Mechanisms 2(3):313-319, 2005.
• Qiao L, MacLean PS, You H, Schaack J, Shao J. Knocking down liver C/EBPα by adenovirus-transduced siRNA improves hepatic gluconeogenesis and lipid homeostasis in db/db mice. Endocrinology 147(6):3060-3069, 2006.
• MacLean PS , Higgins JA, Jackman M, Johnson GC, Fleming-Elder BK, Wyatt H, Melanson EL, Hill JO. Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats. Am J Physiol Regul Integr Comp Physiol 290:1577-1588, 2006.
• Jackman, MR, Kramer R, MacLean PS, Bessesen DH. Trafficking of dietary fat in obesity prone and obesity resistant rats. Am J Physiol Endo Metab (in press, 2006).