Christoph Buettner, MD, PhD Email Christoph Buettner
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- Positions
- PROFESSOR | Medicine, Endocrinology, Diabetes and Bone Disease
- ASSOCIATE PROFESSOR | Neuroscience
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- Language
- English
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- Hospital Affiliation
- The Mount Sinai Hospital
The Buettner Laboratory for Metabolism and Diabetes is studying how and why obesity and diabetes disturb glucose and fat metabolism, impair the action of the hormone insulin, are associated with inflammation and what the role of the brain is in this metabolic dysregulation. One emphasis has been to define brain insulin action in regulating specific metabolic pathways in peripheral organs such as liver and fat, and how nutrients in turn can affect brain function and inflammation. A variety of conditions/diseases impair the regulation of metabolism through the CNS such as Alzheimers, psychiatric diseases, alcohol consumption and stress impair the ability of the brain to control metabolism. In obesity and diabetes the ability of the brain to process important signals from the periphery such as sensing hormones and nutrients is similarly impaired and a major goal of the lab is to restore metabolic control in these conditions by the brain. Approaches that are commonly applied in the lab are to study nutrient partitioning using metabolic tracers during euglycemic clamps in rodents that allow the simultaneous assessment of lipid, glucose and amino acid fluxes. These physiological study techniques are complemented by transcriptional, proteomic and metabolomic analysis to arrive at a molecular understanding of how the brain controls nutrient fluxes in peripheral organs such as liver and adipose tissue.
Team: Andy Shin, PhD Henry Ruiz, PhD Ling Wang, BS Elaine Dellinger, BA Keval Shah, MD Stefanie Chen, MS
Research Topic
Adipose, Brain, Diabetes, Hormones, Inflammation, Insulin, Knockout Mice, Liver, Mass Spectrometry, Mitochondria, Obesity
Multi-Disciplinary Training Area
Neuroscience [NEU]
Education
MD, Ludwig Maximillians University
PhD, Ludwig Maximillians University
Post-Doctoral Fellowship, Brigham and Women's Hospital, Harvard Medical School
Residency, Bellevue Hospital and New York Harbor Health Care Systems, NYU
Clinical Fellowship, Albert Einstein College and Montefiore Hospital
Language
English
2012
Elected to American Society of Clinical Investigation
2012
Mount Sinai Endocrinologist of the Year
2011
Career Development Award
American Diabetes Association
2010
Dr. Harold and Golden Lamport Research Award
2009
Hirschl Award
Hirschl Trust
2007
New York Academy of Science Fellowship Award
2006
Junior Faculty Award
American Diabetes Association
2006
KO8 Award
NIDDK
Type 2 diabetes and obesity are both characterized by impaired metabolic regulation and insulin resistance is a central cause in both of these conditions. The Buettner lab studies the regulation of metabolism and innate immunity through the central nervous system. We employ integrated physiology approaches to deconstruct the role of the brain in orchestrating organ crosstalk such as nutrient flux between adipose tissue and the liver and its relevance in regulating insulin action. A commonly used approach of my lab is to study nutrient partitioning using metabolic tracers during clamps in rodents that allow the simultaneous assessment of lipid, glucose and amino acid fluxes. These physiological study techniques are complemented by transcriptional, proteomic and metabolomic techniques to arrive at a molecular understanding of how the brain controls nutrient fluxes in peripheral organs such as liver and adipose tissue. Previous work from my lab has established that hypothalamic leptin and insulin signaling play important roles in the regulation of adipose tissue lipolysis and lipogenesis. Further, our results obtained so far indicate that hypothalamic insulin and leptin play important roles in regulating hepatic glucose production, VLDL secretion, amino acid metabolism and systemic inflammation. In obesity and diabetes hypothalamic insulin action is impaired in part through increased endocannabinoid tone in the brain, resulting in dysregulated nutrient partitioning and a pro-inflammatory state. Go to the Buettner Laboratory for Metabolism and Diabetes
Our interest is to understand how hormones and nutrients are sensed by the hypothalamus and how the brain controls systemic metabolism. In rodent models of obesity and in type 2 diabetes this brain control of metabolism is impaired and we believe this dysfunction plays an important role in the pathogenesis of both of these conditions. Interestingly, diabetes and obesity are associated with a pro-inflammatory state. We have found that hormones like insulin and leptin regulate systemic inflammation via the brain and the autonomic nervous system and speculate that this may be the basis for the link between impaired metabolic control and inflammation. A commonly used approach in our lab is to study nutrient fluxes with clamp studies combined with metabolic tracers in rodents.
Geer E, Islam J, Buettner C. Mechanisms of Glucocorticoid-Induced Insulin Resistance Focus on Adipose tissue Function and Lipid metabolism. Endocrinol metab Clin N Am Mar; 1(43): 75-102.
Iwen KA, Scherer T, Heni M, Sayk F, Wellnitz T, Machleidt F, Preissl H, Häring HU, Fritsche A, Lehnert H, Buettner C, Hallschmid M. Intranasal insulin suppresses systemic but not subcutaneous lipolysis in healthy humans. The Journal of clinical endocrinology and metabolism 2014 Feb; 99(2).
Shalata A, Ramirez MC, Desnick RJ, Priedigkeit N, Buettner C, Lindtner C, Mahroum M, Abdul-Ghani M, Dong F, Arar N, Camacho-Vanegas O, Zhang R, Camacho SC, Chen Y, Ibdah M, DeFronzo R, Gillespie V, Kelley K, Dynlacht BD, Kim S, Glucksman MJ, Borochowitz ZU, Martignetti JA. Morbid obesity resulting from inactivation of the ciliary protein CEP19 in humans and mice. American journal of human genetics 2013 Dec; 93(6).
Garcia JM, Scherer T, Chen JA, Guillory B, Nassif A, Papusha V, Smiechowska J, Asnicar M, Buettner C, Smith RG. Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice. Endocrinology 2013 Sep; 154(9).
Eissing L, Scherer T, Tödter K, Knippschild U, Greve JW, Buurman WA, Pinnschmidt HO, Rensen SS, Wolf AM, Bartelt A, Heeren J, Buettner C, Scheja L. De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health. Nature communications 2013; 4.
Lindtner C, Scherer T, Zielinski E, Filatova N, Fasshauer M, Tonks NK, Puchowicz M, Buettner C. Binge drinking induces whole-body insulin resistance by impairing hypothalamic insulin action. Science translational medicine 2013 Jan; 5(170).
Fargali S, Scherer T, Shin AC, Sadahiro M, Buettner C, Salton SR. Germline ablation of VGF increases lipolysis in white adipose tissue. The Journal of endocrinology 2012 Nov; 215(2).
Scherer T, Lindtner C, Zielinski E, O'Hare J, Filatova N, Buettner C. Short term voluntary overfeeding disrupts brain insulin control of adipose tissue lipolysis. The Journal of biological chemistry 2012 Sep; 287(39).
Liu J, Zhou L, Xiong K, Godlewski G, Mukhopadhyay B, Tam J, Yin S, Gao P, Shan X, Pickel J, Bataller R, O'Hare J, Scherer T, Buettner C, Kunos G. Hepatic cannabinoid receptor-1 mediates diet-induced insulin resistance via inhibition of insulin signaling and clearance in mice. Gastroenterology 2012 May; 142(5).
Scherer T, Buettner C. Yin and Yang of hypothalamic insulin and leptin signaling in regulating white adipose tissue metabolism. Reviews in endocrine & metabolic disorders 2011 Sep; 12(3).
Scherer T, O'Hare J, Diggs-Andrews K, Schweiger M, Cheng B, Lindtner C, Zielinski E, Vempati P, Su K, Dighe S, Milsom T, Puchowicz M, Scheja L, Zechner R, Fisher SJ, Previs SF, Buettner C. Brain insulin controls adipose tissue lipolysis and lipogenesis. Cell metabolism 2011 Feb; 13(2).
O'Hare JD, Zielinski E, Cheng B, Scherer T, Buettner C. Central endocannabinoid signaling regulates hepatic glucose production and systemic lipolysis. Diabetes 2011 Apr; 60(4).
Li JH, Gautam D, Han SJ, Guettier JM, Cui Y, Lu H, Deng C, O'Hare J, Jou W, Gavrilova O, Buettner C, Wess J. Hepatic muscarinic acetylcholine receptors are not critically involved in maintaining glucose homeostasis in mice. Diabetes 2009 Dec; 58(12).
Muzumdar RH, Huffman DM, Atzmon G, Buettner C, Cobb LJ, Fishman S, Budagov T, Cui L, Einstein FH, Poduval A, Hwang D, Barzilai N, Cohen P. Humanin: a novel central regulator of peripheral insulin action. PloS one 2009; 4(7).
Scherer T, Buettner C. The dysregulation of the endocannabinoid system in diabesity-a tricky problem. Journal of molecular medicine (Berlin, Germany) 2009 Jul; 87(7).
Buettner C, Camacho RC. Hypothalamic control of hepatic glucose production and its potential role in insulin resistance. Endocrinology and metabolism clinics of North America 2008 Dec; 37(4).
Osei-Hyiaman D, Liu J, Zhou L, Godlewski G, Harvey-White J, Jeong WI, Bátkai S, Marsicano G, Lutz B, Buettner C, Kunos G. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J Clin Invest 2008 Sep; 118(9): 3160-9.
Buettner C, Muse ED, Pocai A, Chen A, Kai S, Chen L, Harvey-White J, Kunos G, Rossetti L. Leptin control adipose tissue endocannabinoids and lipogenesis via central, STAT3 independent pathways. Nat Med 2008 Jun; 14(6): 667-675.
Shin AC, Fasshauer M, Filatova N, Grundell LA, Zielinski E, Zhou JY, Scherer T, Lindtner C, White PJ, Lapworth AL, Ilkayeva O, Knippschild U, Wolf AM, Scheja L, Grove KL, Smith RD, Qian WJ, Lynch CJ, Newgard CB, Buettner C. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Cell metabolism 2014 Nov; 20(5).
La Merrill M, Karey E, Moshier E, Lindtner C, La Frano MR, Newman JW, Buettner C. Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring. PloS one 2014; 9(7).
Iwen KA, Scherer T, Heni M, Sayk F, Wellnitz T, Machleidt F, Preissl H, Häring HU, Fritsche A, Lehnert H, Buettner C, Hallschmid M. Intranasal insulin suppresses systemic but not subcutaneous lipolysis in healthy humans. The Journal of clinical endocrinology and metabolism 2014 Feb; 99(2).
Garcia JM, Scherer T, Chen JA, Guillory B, Nassif A, Papusha V, Smiechowska J, Asnicar M, Buettner C, Smith RG. Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice. Endocrinology 2013 Sep; 154(9).
Eissing L, Scherer T, Tödter K, Knippschild U, Greve JW, Buurman WA, Pinnschmidt HO, Rensen SS, Wolf AM, Bartelt A, Heeren J, Buettner C, Scheja L. De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health. Nature communications 2013; 4.
Lindtner C, Scherer T, Zielinski E, Filatova N, Fasshauer M, Tonks NK, Puchowicz M, Buettner C. Binge drinking induces whole-body insulin resistance by impairing hypothalamic insulin action. Science translational medicine 2013 Jan; 5(170).
Scherer T, Lindtner C, Zielinski E, O'Hare J, Filatova N, Buettner C. Short term voluntary overfeeding disrupts brain insulin control of adipose tissue lipolysis. The Journal of biological chemistry 2012 Sep; 287(39).
Scherer T, O'Hare J, Diggs-Andrews K, Schweiger M, Cheng B, Lindtner C, Zielinski E, Vempati P, Su K, Dighe S, Milsom T, Puchowicz M, Scheja L, Zechner R, Fisher SJ, Previs SF, Buettner C. Brain insulin controls adipose tissue lipolysis and lipogenesis. Cell metabolism 2011 Feb; 13(2).
O'Hare JD, Zielinski E, Cheng B, Scherer T, Buettner C. Central endocannabinoid signaling regulates hepatic glucose production and systemic lipolysis. Diabetes 2011 Apr; 60(4).
Buettner C, Muse ED, Cheng A, Chen L, Scherer T, Pocai A, Su K, Cheng B, Li X, Harvey-White J, Schwartz GJ, Kunos G, Rossetti L, Buettner C. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nature medicine 2008 Jun; 14(6).
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Buettner during 2017 and/or 2018. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Consulting:
- Guidepoint Global
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