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United States Department of Agriculture

Agricultural Research Service

Sean Adams

Research Leader

 

 

Ph.D., Department of Nutritional Sciences 

University of Illinois

 

Office:     430 West Health Sciences Dr.

                 University of California

                 Davis, CA 95616

             

Phone:     (530) 754-4417 (office)

                 (530) 754-5779 (lab)

 

Fax:         (530) 752-5271

 

 

Adams Lab

                                                                                              

                                                                              

 

  

Biography

Born and raised in California, Dr. Adams attended Fresno State University where he earned a B.A. in Biology and a Minor in Chemistry.  His interest in comparative physiology led to an M.S. in Marine Sciences at UC, Santa Cruz, where he worked in the lab of Dr. Dan Costa to study metabolic and renal adaptations associated with natural long-term fasting in seals.  In the group of Dr. Jack Odle at the University of Illinois, his Ph.D. research in Nutritional Sciences explored the regulation of intracellular fatty acid trafficking and combustion in the neonatal piglet model. This work helped highlight the importance of hydrolysis of acetyl-CoA (e.g., acetogenesis) as a common biochemical fate of lipids in the cell.  During an NSF/NATO Postdoctoral Fellowship with Dr. Fausto G. Hegardt at the University of Barcelona, he investigated the molecular regulation of ketone body production through investigations of postnatal gene expression of the key ketogenic enzyme mitochondrial hydroxymethylglutaryl-CoA synthase (HMG-CoA synthase).  As a postdoctoral investigator with Dr. J. Denis McGarry at UT Southwestern Medical School in Dallas, Dr. Adams evaluated the potential role of carnitine palmitoyltransferase (CPT) in male reproductive function through analysis of expression and activity levels in developing germ cells, and he built a variety of CPT adenoviral delivery tools used to study fatty acid metabolism in muscle and liver. Prior to joining the WHNRC, Dr. Adams worked in the biotechnology and pharmaceutical research arena for over seven years, focusing on molecular and biochemical events associated with tissue thermogenesis and energy expenditure.  Research included studies of unique mitochondrial uncoupling proteins (UCPs) and carrier proteins implicated in mitochondrial metabolism, characterization of genes and metabolic pathways involved in brown adipose tissue (BAT) heat production and nutrient utilization, and evaluation of food intake physiology through exploration of the activities of gut hormones such as peptide YY (PYY) and ghrelin.  His recent work builds upon this background to better understand the physiological networks that shape metabolic status.

Research Program

The laboratory of Dr. Adams investigates the etiology of obesity and associated disorders such as diabetes, determines how specific foods and food components modify these parameters, and searches for molecular biomarkers reflective of a healthy or disordered metabolism.  Current Research areas include:

·          Interrelationships between fat tissue, metabolic status, and the peripheral nervous system--Interestingly, there are a number of proteins uniquely co-expressed in both peripheral nerves and fat cells, suggestive of shared function and potential cross-talk between fat and afferent neural circuits relaying information to the brain.  Studies are underway to test how expression of these unusual “fat-neuron” genes impact and are influenced by obesity and specific metabolite and hormone cues.

·          Identification of New Markers of Diabetes--Unfortunately, most people at risk of developing type 2 diabetes mellitus are not identified early enough to thwart disease through nutritional or other interventions.  The lab is leading a collaborative effort involving scientists at the WHNRC, UC Davis, the University of Alabama at Birmingham, the University of Ottawa, and Case Western Reserve University to identify hundreds of metabolites and small molecules in biofluids such as blood plasma to unmask patterns indicative of insulin resistance and poor blood glucose control.  Efforts also focus on muscle-specific metabolites that correlate with markers of blood glucose homeostasis and that reflect fat metabolism.

·          Obesity- and Diabetes-Associated Inflammation in Fat Tissue and Effects of Specific Foods and Metabolites to Modulate Inflammation and Metabolic Profiles--Obesity is a major risk factor for development of metabolic disease, and it is now believed that inflammation is at the heart of this phenomenon.  Type 2 diabetes is also in part a disease of increased inflammation.  One line of research examines how obesity and diet correlate with fat tissue infiltration of macrophages.  Other work is determining whether certain metabolites that accumulate in the blood of type 2 diabetics evoke a pro-inflammatory response associated with insulin resistance.

Research Accomplishments

·         The team has identified two cellular proteins that share the unusual property of abundant co-expression in fat cells and in neurons involved with signaling information from peripheral tissues to the brain.  Such a pattern suggests that these otherwise quite different biological systems share important functional attributes.  The genes encoding these proteins are responsive to the critical metabolic regulator PPAR, potentially highlighting a mechanism by which metabolic status can be sensed by or alter activities in peripheral nerves.

·          Working with groups from the WHNRC, UC Davis, the University of Ottawa, the University of Alabama Birmingham, and Case Western Reserve University, metabolite patterns indicative of poor blood sugar control have been identified by leveraging the emerging field of metabolomics.  These studies have shown that in type 2 diabetics, there are increased plasma concentrations of certain acylcarnitines and amino acid moieties that reflect inefficient fatty acid ß-oxidation (“fat burning”) and abnormal amino acid catabolism.  The latter may impact the primary energy-generating process in the cell, the tricarboxylic acid cycle.

·         Inflammation in fat tissue is an important contributor to poor metabolic health, but the specific nutrients and foods that can impact immune cell (macrophage, e.g.) infiltration into adipose tissue remains unclear.  The lab has identified a new marker of macrophage infiltration in fat, termed CD11d, and has found evidence that the degree of macrophage infiltration tracks body weight gain differences in lean-to-obese mice.  The latter provides evidence that as energy storage requirements increase, macrophage activities in fat likely play a normal, non-pathological role in adipose tissue remodeling.  Further, studies using dairy protein/carbohydrate in a high fat obesity-promoting diet showed that dairy components thwart obesity and adipose inflammation--this indicates that specific diet factors can have a profound effect on these processes.

Selected Articles & Patent Applications

1.      A.P. Thomas, T.N. Dunn, P.J. Oort, M. Grino, and S.H. Adams.  Inflammatory phenotyping identifies CD11d as a gene markedly induced in white adipose tissue in obesity.  J. Nutr., in press.

 

2.      J.Q. Purnell JQ, B.A. Klopfenstein, A.A. Stevens, P.J. Havel, S.H. Adams, T.N.Dunn, C. Krisky, and W.D. Rooney.  Brain fMRI response to glucose and fructose infusions in humans.  Diabetes Obes Metab. 2010 Nov 19.doi:10.1111/j.1463-1326.2010.01340.x. [Epub ahead of print]

 

3.      O. Fiehn, W.T. Garvey, J.W. Newman, K.H. Lok, C.L. Hoppel, and S.H. Adams*.  Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women.  PLoS ONE 5(12): e15234, 2010

 

4.      E. Seifert, O. Fiehn, V. Bezaire, D.B. Bickel, G. Wohlgemuth, S.H. Adams*, and M-E. Harper*.  Long-chain fatty acid combustion rate is associated with unique metabolite profiles in skeletal muscle mitochondria. (*co-corresponding authors)  PLoS One 5(3): e9834, 2010 

 

5.      T.A. Knotts, H.W. Lee, J.B. Kim, P.J. Oort, R. McPherson, R. Dent, K. Tachibana, T. Doi, S. Yu, J.K. Reddy, K. Uno, H. Katagiri,  M. Pasarica, S.R. Smith, D.D. Sears, M. Grino, and S.H. Adams.  Molecular characterization of the tumor suppressor candidate 5 gene:  regulation by PPARγ and identification of TUSC5 coding variants in lean and obese humans.  PPAR Research, vol. 2009, Article ID 867678, 13 pages, doi:10.1155/2009/867678, 2009

 

6.      C.M. Mack, C.J. Soares, J.K. Wilson, J.R. Athanacio, V.F. Turik, J.L. Trevaskis, J.D. Roth, P.A. Smith, B. Gedulin, C.M. Jodka, B.L. Roland, S.H. Adams, A. Lwin, J. Herich, K.D. Laugero, C. Vu, R. Pittner, J.R.   Paterniti Jr., M. Hanley, S. Ghosh, D.G. Parkes.  Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight. Int. J. Obesity  2009 Nov 24. [Epub ahead of print]

 

7.  S.H. Adams*, C.L. Hoppel, K.H. Lok, L. Zhao, S.W. Wong, P.E. Minkler, D.H. Hwang, J.W. Newman, and W.T Garvey*.  Plasma acylcarnitine profiles suggest incomplete long chain fatty acid β-oxidation and altered tricarboxylic cycle activity in type 2 diabetic African-American women. (*co-corresponding authors)J. Nutr. 139(6):1073-81, 2009

 

8.      G. Paulino, C.B. de la Serre, T.A. Knotts, P.J. Oort, J.W.Newman, S.H. Adams, and H.E. Raybould. Increased expression of receptors for orexigenic factors in nodose ganglion of diet-induced obese rats.  Am. J.Physiol. Endocrinol. Metab. 296(4): E898-903, 2009

 

9.      K.L. Teff, J. Grudziak, R.R. Townsend, T.N. Dunn, R.W. Grant, S.H. Adams, K.L. Stanhope, and P.J. Havel. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women:influence of insulin resistance on plasma triglyceride responses. J. Clin.Endocrin.Metab. 94(5):1562-9, 2009

 

10.  S.H. Adams, K.L. Stanhope, R.W. Grant, B.P. Cummings, and P.J. Havel.  Metabolic and endocrine profiles in response to systemic infusion of fructose and glucose in rhesus macaques.  Endocrinology 149(6):3002-8, 2008.

 

11.  Oort, P.J., T.A. Knotts, M. Grino, N. Naour, J-P. Bastard, K. Clément, N. Ninkina, V.L. Buchman, P.A.    Permana, X. Luo, G. Pan, T.N. Dunn, and S.H. Adams.  γ-Synuclein is an adipocyte-neuron gene coordinately-expressed with leptin and increased in human obesity.  J. Nutr. 138(5):841-848, 2008

 

12.  Oort, P.J.,C.H.Warden, T.K. Baumann, T.A. Knotts, and S.H. Adams. Characterization of Tusc5, an adipocyte gene co-expressed in peripheral neurons.  Mol. Cell. Endocrinol. 276(1-2):24-35, 2007. Epub 2007 Jul 1

  

13.  S. H. Adams, C. Lei, C.M. Jodka, S.E. Nikoulina, J.A. Hoyt, B. Gedulin, C.M. Mack, and E.S. Kendall. PYY[3-36] administration decreases the respiratory quotient & reduces adiposity in diet-induced obese mice.  J. Nutr. 136:  195-201, 2006

 

14.  S.H. Adams, Wesley B. Won, S.E. Schonhoff, A.B. Leiter, and J.R. Paterniti, Jr.  Effects of PYY[3-36] on short-term food intake in mice are not affected by prevailing plasma ghrelin levels. Endocrinology 145:4967-4975, 2004

 

15.  G. Perdomo, S.R. Cummerford, S.H. Adams, R.M. O’Doherty, and N.F. Brown.  Increased ß-oxidation in muscle cells enhances insulin-stimulated glucose metabolism and protects against fatty acid induced insulin resistance despite intramyocellular lipid accumulation.  J. Biol. Chem. 279(26):27177-27186, 2004

 

16.  Fu, L., L. John, S.H. Adams, X.X. Yu, E. Tomlinson, M. Renz, P.M. Williams, R. Soriano, R. Corpuz, M. Moffat, R. Vandlen, L. Simmons, J. Foster, J-P. Stephan, S.P. Tsai, and T.A. Stewart.  Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin deficient diabetes.  Endocrinology      145(6):2594-2603, 2004

 

17.  Yu, X.X., D.A. Lewin, W. Forrest, & S.H. Adams. Cold elicits the simultaneous induction of fatty acid synthesis & b-oxidation in rodent brown adipose tissue.  Prediction from differential gene expression & confirmation in vivo.  FASEB J. 16: 155-168, 2002

 

18.  Adams, S.H., C. Chui., S.L. Schilbach, X.X. Yu, A.D. Goddard, J.C. Grimaldi, J. Lee, P. Dowd, S. Colman, & D.A. Lewin.  BFIT, a unique acyl-CoA thioesterase induced in thermogenic brown adipose tissue. Cloning, organization of the human gene, & assessment of a potential link to obesity.  Biochem. J. 360: 135-142, 2001

 

19.  Adams, S.H., G. Pan, & X.X. Yu.  Perspectives on the biology of UCP homologues.  Invited contribution for Biochem. Soc. Transactions 29(6): 798-802, 2001

  

20.  Yu, X.X., D.A. Lewin, A. Zhong, J. Brush, P.W. Schow, S.W. Sherwood, G. Pan, & S.H. Adams*. Overexpression of the human 2-oxoglutarate carrier lowers mitochondrial membrane potential in HEK-293 cells: contrast with the unique cold-induced mitochondrial carrier CGI-69.  Biochem. J. 353: 369-375, 2001

 

21.  Adams, S.H. Uncoupling protein homologs:  emerging views of physiological function. Invited Review for Recent Advances in Nutritional Sciences. J. Nutr. 130:  711-714, 2000

 

22.  Yu, X.X., J.L. Barger, B.B. Boyer, M.D. Brand, G. Pan, and S.H. Adams.  Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, & mitochondrial proton leak kinetics.  Am. J. Physiol.     Endocrinol. Metab. 279:  E433-446, 2000

 

23.  Yu, X.X., W. Mao, A. Zhong, P. Schow, J. Brush, S.W. Sherwood, S.H. Adams, and G. Pan.  Characterization novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation.  FASEB J. 14(11):  1611-1618, 2000

 

24.  Mao, W., X.X. Yu, A. Zhong, W. Li, J. Brush, S.W. Sherwood, S.H. Adams, and G. Pan.  UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells.  FEBS Letters 443: 326-330, 1999.

 

25.  Adams, S.H., V. Esser, N.F. Brown, N.H. Ing, L . Johnson, D.W. Foster, and J.D. McGarry. Expression and possible role of muscle-type carnitine palmitoyltransferase I during sperm development in the rat.  Biol. of Reprod. 59: 1399-1405, 1998

 

26.  Adams, S.H. and J. Odle. Acetogenesis does not replace ketogenesis in fasting piglets infused with hexanoate. Am. J. Physiol. Endocrinol. Metab.  274:  E963-E970, 1998

 

27.  Adams, S.H., C. Sampaio Alho, G. Asins, F.G. Hegardt, and P.F. Marrero.  Gene expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in a poorly ketogenic mammal:  effect of starvation during the neonatal period of the piglet.  Biochem. J. 324:  65-73, 1997

 

28.  Adams, S.H., X. Lin, X.X. Yu, J. Odle, and J.K. Drackley.  Hepatic fatty acid metabolism in pigs and rats: major differences in endproducts, O2 uptake, and b-oxidation. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 272: R1641-R1646,  1997

 

29.  Lin, X., S.H. Adams, and J. Odle.  Acetate represents a major product of heptanoate and octanoate b-oxidation in hepatocytes isolated from neonatal piglets.  Biochem. J. 318: 235-240, 1996

 

30.  Ortiz, R.M., S.H. Adams, D.P. Costa, and C.L. Ortiz. Plasma vasopressin levels and water conservation in fasting, postweaned northern elephant seal pups (Mirounga angustirostris).  Marine Mammal Sci. 12: 99-106, 1996

 

31.  Odle, J., T.A.T.G. van Kempen, J.K. Drackley, and S.H. Adams.  Carnitine palmitoyltransferase modulation of hepatic fatty acid metabolism and radio-HPLC evidence for low ketogenesis in neonatal pigs.  J. Nutr. 125:  2541-2549, 1995

 

32.  Tetrick, M.A., S.H. Adams, J. Odle, and N.J. Benevenga.  Contribution of D-(-)-3-hydroxybutyrate to the energy expenditure of neonatal pigs.  J. Nutr. 125:  264-272, 1995

 

33.  Patterson-Buckendahl, P., S.H. Adams, R. Morales, W.S.S. Jee, C.E. Cann, and C.L. Ortiz. Skeletal development in newborn and weanling northern elephant seals.  Am. J. Physiol. Regulatory Integrative Comp. Physiol. 267:  R726-R734, 1994

 

34.  Adams, S.H. and J. Odle. Plasma b-hydroxybutyrate after octanoate challenge:  attenuated ketogenic capacity in neonatal swine. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 265:  R761-R765, 1993

 

35.  Adams, S.H. and D.P. Costa.  Water conservation and protein metabolism in northern elephant seal pups during the postweaning fast.  J. Comp. Physiol. B 163:  367-373, 1993

 

36.    Adams, S.H., D.P. Costa, & S.C. Winter.  Plasma carnitine in fasting neonatal and adult northern elephant seals. Am. J. Physiol. Endocrinol. Metab.  263:  E570-E574, 1992

 

 

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Last Modified: 11/17/2011