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Christoph Buettner

  • ASSOCIATE PROFESSOR Medicine, Endocrinology, Diabetes and Bone Disease
  • ASSOCIATE PROFESSOR Neuroscience
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Training Areas

Research

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.

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.

Publications

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.

Industry Relationships

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.

Dr. Buettner did not report having any of the following types of financial relationships with industry during 2013 and/or 2014: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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