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
· 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.
· 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
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,
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
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
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.
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