eBriefing

Nutrient Sensing: How the Brain and Gut Regulate Food Intake

Nutrient Sensing
Reported by
Alan Dove

Posted April 09, 2009

Overview

Maintaining a careful balance between stored energy and caloric intake is important to ensure that the body has enough energy to maintain itself, grow, and engage in activity. When balanced improperly, obesity and its accompanying disorders can result. The recent explosion in rates of diabetes and obesity worldwide suggests that humans are increasingly unable to maintain proper levels of intake and expenditure.

This meeting considered a range of work exploring the biology of hunger, in particular the complex signaling pathways that regulate metabolism. Speakers discussed the physiology of nutrient sensing, pathways through which the gut and the central nervous system communicate to sense hunger (including the TOR pathway and hexosamine signaling pathway), the possible role of glial cells in regulating food intake, how differences in bacterial populations in the gut might contribute to weight gain, and comparative approaches between humans and other organisms that are producing new insights into this issue.

Use the tabs above to find a meeting report and multimedia from this event.

Articles

James Brown

Hou C, Zuo W, Moses ME, et al. 2008. Energy uptake and allocation during ontogeny. Science 322: 736-739.

Payne JL, Boyer AG, Brown JH, et al. 2009. Two-phase increase in the maximum size of life over 3.5 billion years reflects biological innovation and environmental opportunity. Proc. Natl. Acad. Sci. USA 106: 24-27. Full Text

Sibly RM, Brown JH. 2007. Effects of body size and lifestyle on evolution of mammal life histories. Proc. Natl. Acad. Sci. USA 104: 17707-17712. Full Text

John A. Hanover

Chen S, Whetstine JR, Ghosh S, et al. 2009. The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span. Proc. Natl. Acad. Sci. USA 106: 1496-1501.

Forsythe ME, Love, DC, Lazarus BD, et al. 2006. Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 (O-GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer. Proc. Natl. Acad. Sci. USA 103: 11952-11957. Full Text

Kim EJ, Amorelli B, Abdo M, et al. 2007. Distinctive inhibition of O-GlcNAcase isoforms by an alpha-GlcNAc thiolsulfonate. J. Am. Chem. Soc. 129: 14854-14855.

Shai Shaham

Bacaj T, Tevlin M, Lu Y, Shaham S. 2008. Glia are essential for sensory organ function in C. elegans. Science 322: 744-747.

Heiman MG, Shaham S. 2007. Ancestral roles of glia suggested by the nervous system of Caenorhabditis elegans. Neuron Glia Biol. 3: 55-61.

Yoshimura S, Murray JI, Lu Y, et al. 2008. mls-2 and vab-3 Control glia development, hlh-17/Olig expression and glia-dependent neurite extension in C. elegans. Development 135: 2263-2275. Full Text

Ruth E. Ley

Ley RE, Hamady M, Lozupone C, et al. 2008. Evolution of mammals and their gut microbes. Science 320: 1647-1651. Full Text

Turnbaugh PJ, Hamady M, Yatsunenko T, et al. 2009. A core gut microbiome in obese and lean twins. Nature 457: 480-484.

Wen L, Ley RE, Volchkov PY, et al. 2008. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455: 1109-1113.

Gary J. Schwartz

Blouet C, Ono H, Schwartz GJ. 2008. Mediobasal hypothalamic p70 S6 kinase 1 modulates the control of energy homeostasis. Cell Metab. 8: 459-467.

Madsen AN, Jelsing J, van de Wall EH, et al. 2009. Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents. Neurosci. Lett. 449: 20-23.

Schwartz GJ, Fu J, Astarita G, et al. 2008. The lipid messenger OEA links dietary fat intake to satiety. Cell Metab. 8: 281-288.

Randy J. Seeley

Cota D, Matter EK, Woods SC, Seeley RJ. 2008. The role of hypothalamic mammalian target of rapamycin complex 1 signaling in diet-induced obesity. J. Neurosci. 28: 7202-7208.

Proulx K, Cota D, Woods SC, Seeley RJ. 2008. Fatty acid synthase inhibitors modulate energy balance via mammalian target of rapamycin complex 1 signaling in the central nervous system. Diabetes 57: 3231-3238. Full Text

Sandoval DA, Bagnol D, Woods SC, et al. 2008. Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake. Diabetes 57: 2046-2054. Full Text

John Kral

Kaufman D, Shorman I, Banerji MA, et al. 2007. Early-life stress and the development of obesity and insulin resistance in juvenile bonnet monkeys. Diabetes 56: 1382-1386. Full Text

Kral JG, Biron S, Simard S, et al. 2006. Large maternal weight loss from obesity surgery prevents transmission of obesity to children followed 2-18 yrs. Pediatrics 118: e1644-e1649. Full Text

Levitt DG, Heymsfield SB, Pierson RN Jr., et al. 2007. Physiological models of body composition and human obesity. Nutr. Metab. (Lond). 4:19. Full Text

Rising R, Signaev M, Rosenblum LA, et al. 2008. Energy expenditure in chow-fed female non-human primates of various weights. Nutr. Metab. (Lond). 5: 32. Full Text

Speakers

James H. Brown, PhD

University of New Mexico
e-mail | web site | publications

James Brown is distinguished professor of biology at the University of New Mexico. Brown received his PhD from the University of Michigan. He has held faculty appointments at the University of California at Los Angeles, University of Utah, University of Arizona, University of New Mexico, and Santa Fe Institute. In 1977 Brown began a still-ongoing experimental field study of interactions among desert rodents, ants, and plants. In the late 1980s, he pioneered a research program called "macroecology" to understand pervasive patterns in the body sizes, abundances, and distributions of species. In 1997 Brown, his student Brian Enquist, and physicist Geoffrey West published a seminal paper on why metabolic rate scales as the 3/4 power of body mass. This has led to interdisciplinary research on biological scaling and the metabolic basis of ecology.

Brown has published 7 books and more than 200 papers and book chapters, mentored 60 PhD students and 25 postdocs, served as president of four scientific societies, and received many awards and honors, including the MacArthur and Odum Awards from the Ecological Society of America, the Marsh Award from the British Ecological Society, and election to the U.S. National Academy of Sciences.

John A. Hanover, PhD

NIDDK, NIH
e-mail | web site | publications

John Hanover is chief of the Laboratory of Cell Biochemistry and Biology at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health. In 1976 he joined the PhD program in the Physiological Chemistry Department then headed by Albert Lehninger at Johns Hopkins University School of Medicine. He examined the role of activated sugars in glycoprotein assembly with William J. Lennarz as his graduate mentor. He then did a Jane-Coffin Childs Memorial Fellowship with Ira Pastan, studying growth factor regulation and the cell biology of intracellular trafficking. Hanover joined the NIH laboratory founded by Arthur Kornberg, LBM, NIDDK in 1984 (Chief: Bill Jakoby). As an independent investigator in LBM, he pioneered the biochemical examination of nuclear pores, the mechanism of nuclear transport, and discovered the hexosamine signaling pathway now thought to play a role in Diabetes mellitus and neurodegeneration. He is currently the subgroup leader of Glycans in Development and Physiology, a 25-member group affiliated with the Consortium for Functional Glycomics.

Hanover has been a faculty of the Foundation for Advanced Education in the Sciences (FAES) since 1983. He is now chairman of the Biochemistry and Biophysics Department in the FAES. He has also participated in a number of FAES courses over the years as a lecturer. Hanover is also an adjunct faculty at Johns Hopkins University, George Washington University, Georgetown University, and Catholic University.

Shai Shaham, PhD

The Rockefeller University
e-mail | web site | publications

Shai Shaham is an associate professor at the Rockefeller University in New York. He received his PhD in biology from the Massachusetts Institute of Technology in 1995 and completed postdoctoral studies at the University of California, San Francisco, with the late Ira Herskowitz and with Cori Bargmann. Shaham is the recipient several awards, including a Breast Cancer Alliance Masin Young Investigator Award, a Klingenstein Fellowship Award in the Neurosciences, a Sidney Kimmel Foundation for Cancer Research Scholarship, a Brookdale Foundation National Fellowship, and a Helen Hay Whitney Foundation Postdoctoral Fellowship.

The Shaham lab has two distinct areas of interest: understanding how programmed cell death is regulated during animal development; and how glial cells influence nervous system development and function. Using genetic approaches in the roundworm Caenorhabditis elegans, the Shaham lab has identified regulators of apoptosis, a common form of cell death. They have also described a novel, morphologically conserved cell death program with intriguing similarities to programs promoting neurodegenerative disorders. The Shaham lab's work on glia in C. elegans has revealed important roles for these cells in regulating neuron shape and function, and has suggested that glia also have neuron-independent roles in regulating an animal's response to its environment.

Ruth E. Ley, PhD

Cornell University
e-mail | web site | publications

Ruth Ley is an assistant professor at Cornell University. Ley earned a BA in Integrative Biology from the University of California, Berkeley. Her graduate training was at the University of Colorado Boulder with Steven Schmidt. Ley was an NRC postdoctoral research associate with Norman Pace at the University of Colorado, Boulder from 2001–2004. Her postdoctoral training continued with Jeffrey Gordon at Washington University School of Medicine's Center for Genome Science from 2004–2008. During this time she investigated the role of gut microbes in obesity and type 1 diabetes, and investigated the links between diet and host genotype in gut microbes in the context of mammalian evolution. She was an assistant research professor in the Department of Developmental Biology at Washington University School of Medicine from 2007–2008.

Gary J. Schwartz, PhD

Albert Einstein College of Medicine of Yeshiva University
e-mail | web site | publications

Gary Schwartz is a professor of medicine and neuroscience at the Albert Einstein College of Medicine of Yeshiva University. His basic research focuses on the neurobiology of feeding behavior, energy balance, and glucose homeostasis in obesity and diabetes. He has published extensively on the role of gut-brain communication in the control of food intake and metabolism, and is a member of the editorial board of several related journals, including the American Journal of Physiology, Physiology and Behavior, and Endocrinology. He is a senior member and Core leader for the Albert Einstein Diabetes Research and Training Center and the New York Obesity Research Center, and is the director of the Skirball Institute for Nutrient Sensing.

Randy J. Seeley, PhD

University of Cincinnati College of Medicine
e-mail | web site | publications

Randy Seeley is professor of psychiatry and associate director of the Obesity Research Center at the University of Cincinnati College of Medicine. His work has focused on the actions of various peripheral hormones in the CNS that serve to regulate food intake and body weight. In particular, he has focused upon the numerous hypothalamic and G.I. peptides and their associated receptors that influence both energy intake and energy expenditure.

Seeley received his PhD from the University of Pennsylvania in 1993. He then spent two years as a fellow and two years on the faculty at the University of Washington before locating to the University of Cincinnati in 1997. He has published over 150 peer-reviewed articles including articles in Science, Nature, Nature Medicine, Nature Neuroscience Reviews, The Journal of Clinical Investigation, and the New England Journal of Medicine. He is also the author of 12 book chapters and co-edited a volume on macronutrient selection. He also is the recipient of the 2003 Lilly Scientific Achievement award from the North American Association for the Study of Obesity given to the individual with the highest level of scientific achievement in obesity research in North America less than 15 years after their terminal degree.

John Kral, MD, PhD

SUNY Downstate
e-mail | web site | publications

John Kral received his MA in Education and Behavioral Neuroscience in 1961, his MD in 1967, completed surgical residency in 1972 and defended his PhD thesis: "Surgical reduction of Adipose Tissue" in 1976 at the University of Göteborg, Sweden. While there, he participated in establishing the program for surgical treatment of obesity, with a broad range of clinical research studies on integrative metabolic physiology including hepatic lipid metabolism, appetite regulation, vagus nerve function, and body composition.

In 1980 he was recruited to St. Luke's Hospital Center, Columbia University to develop a program of surgical metabolism and anti-obesity surgery. He is a charter member of NAASO—the Obesity Society and a co-founder of the American Society for Bariatric Surgery in 1983.

In 1988 Kral moved to SUNY Downstate as professor of surgery and director of surgical services at KCHC. While at Downstate he has initiated and co-organized the NIH Consensus Development Conference Gastrointestinal Surgery for Severe Obesity in 1991, served as president of the NY State Society of Surgeons from 1995 to 1997, was co-chairman of the NIH Workshop Research Considerations in Obesity Surgery in 2001, and served on numerous scientific organizing committees, editorial boards, and in scientific societies.


Alan Dove

Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism, and blogs at http://dovdox.com.