help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology, doi:10.1210/en.2007-0776
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kalsbeek, A.
Right arrow Articles by Buijs, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kalsbeek, A.
Right arrow Articles by Buijs, R. M.
Endocrinology Vol. 148, No. 12 5635-5639
Copyright © 2007 by The Endocrine Society

Minireview: Circadian Control of Metabolism by the Suprachiasmatic Nuclei

Andries Kalsbeek, Felix Kreier, Eric Fliers, Hans P. Sauerwein, Johannes A. Romijn and Ruud M. Buijs

Netherlands Institute for Neuroscience (A.K., F.K.), 1105 BA Amsterdam, The Netherlands; Department of Endocrinology and Metabolism (E.F., H.P.S.), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Endocrinology and Metabolism (J.A.R.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Instituto de Investigaciones Biomedicas (R.M.B.), Universidad Autonoma Mexico, Apartado Postal 70228, Ciudad Universitaria, 04510 Mexico D.F.

Address all correspondence and requests for reprints to: Andries Kalsbeek, Netherlands Institute for Neuroscience, Hypothalamic Integration Mechanisms, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands. E-mail: a.kalsbeek{at}nin.knaw.nl.


   Abstract
Top
 Abstract
Introduction
 SCN Outputs
 Balancing SCN Outputs
 The SCN and the...
 Social Jetlag
 References
 
In the present review, first we present the anatomical connections used by the mammalian biological clock to enforce its endogenous rhythmicity on the rest of the body, especially the energy homeostatic systems. Subsequently, we present a number of physiological experiments investigating the functional significance of this neuroanatomical substrate. Together, this overview of experimental data, for a major part derived from our own experiments, reveals a highly specialized organization of connections between the endogenous pacemaker and both the presympathetic and pre-parasympathetic hypothalamic systems, providing the biological clock with a unique opportunity to modulate the balance of sympathetic/parasympathetic inputs to peripheral organs. We hypothesize that a well-balanced autonomic nervous input, differentiated according to the time of day and the body compartment, is an important companion to withstand the progressive burden of the current 24/7 society on our health and well-being.


   Introduction
Top
 Abstract
 Introduction
SCN Outputs
 Balancing SCN Outputs
 The SCN and the...
 Social Jetlag
 References
 
IN THE PREMODERN WORLD, temporal cycles of hunger and satiety matched the patterns of sleep and wakefulness that occurred during the alternating periods of light and darkness as dictated by the recurrent rise and fall of the sun. In mammals, an autonomous endogenous clock in the brain has developed to coordinate and anticipate our behavior and the metabolism in our peripheral tissues according to this environmental periodicity as it is fixed in geophysical time by the rotation of the earth around its axis. The mammalian biological clock, located in the suprachiasmatic nuclei (SCN) of the ventral hypothalamus, is composed of several sets of small and densely packed neurons in which different (peptidergic) transmitters are expressed. The cell-autonomous clock mechanism of these neurons has been demonstrated by recording circadian rhythms of electrical firing from individual neurons and is dependent on the action of circadian clock genes. The ultimate expression of circadian rhythms is supposed to be the result of the expression of so-called clock-controlled genes, among which is one of the peptidergic SCN transmitters, i.e. vasopressin (VP). A proper entrainment of this endogenous clock mechanism to the outside world is ensured by a number of input signals of which, depending on the situation, light and (feeding) activity are the most important ones. Subsequently, the rhythmic output of this endogenous clock is conveyed to the milieu intérieur by both the neuroendocrine and autonomic nervous system (ANS). Here we discuss our hypothesis that in today’s modern society, the output of our biological clock is unbalanced due to insufficient or even contradictory input signals, hampering its proper entrainment to the outside world.


   SCN Outputs
Top
 Abstract
 Introduction
 SCN Outputs
Balancing SCN Outputs
 The SCN and the...
 Social Jetlag
 References
 
The pronounced day/night rhythm in cerebrospinal fluid VP was the first SCN output to be characterized (1). These circadian fluctuations of VP release from the SCN are a result of the day/night rhythm in the firing rate of VP-containing SCN neurons (2, 3). Meanwhile, many other SCN transmitters have been recognized (4). Most of these neurotransmitters also show a clear day/night rhythm in the amount of protein or mRNA, but to date, VP is still the only SCN output that has been demonstrated to be secreted in a circadian rhythm in vivo. Transplantation and parabiosis experiments unequivocally demonstrated that nonneuronal mechanisms are not sufficient to reinstate circadian rhythms in all peripheral organs (5, 6, 7). Moreover, an elegant experiment by de la Iglesia et al. (8) provided clear functional evidence for the necessity of point-to-point neural connections to sustain neuroendocrine rhythms. Information on the distribution of SCN projections was initially obtained from neuroanatomical studies using tracing, immunocytochemistry, SCN lesions, or a combination of these methods (9, 10). All these studies showed that the outflow of SCN information mainly pertained to the medial hypothalamus, with most of the SCN projections being directed toward target areas that contain mainly interneurons, such as the medial preoptic area, dorsomedial hypothalamus, and sub-paraventricular nucleus (sub-PVN). Although much more scarce, direct connections to neuroendocrine neurons (i.e. CRH-, TRH-, tyrosine hydroxylase-, and GnRH-containing) in the PVN, arcuate nucleus, and medial preoptic area, and preautonomic neurons in the PVN were described as well (11, 12). In a series of microinfusion studies we have been able to show how the SCN uses the point-to-point neural connections to its different target areas to control peripheral rhythms in hormone release (13, 14).


   Balancing SCN Outputs
Top
 Abstract
 Introduction
 SCN Outputs
 Balancing SCN Outputs
The SCN and the...
 Social Jetlag
 References
 
The above mentioned experiments revealed, among others, that the activity of preautonomic PVN neurons, which are in charge of the circadian rhythm of pineal melatonin release, are controlled by a balance of glutamatergic and GABAergic inputs from the SCN. A similar control mechanism also seems to exist for the circadian rhythm in plasma glucose concentrations. In this case, it is the activity of preautonomic PVN neurons connected to the sympathetic innervation of the liver, and dedicated to the control of hepatic glucose production, that is determined by a balance of GABAergic and glutamatergic inputs (15). As clearly indicated by a series of retrograde viral tracing studies, for instance from adipose tissue (both brown and white), pancreas, stomach, and intestines, a similar SCN control of other peripheral tissues involved in energy metabolism can be imagined as well (16, 17, 18). Moreover, the recent studies of Pocai and co-workers (19) once again stressed the important role of the hypothalamus in energy metabolism. We hypothesized that part of the action of the SCN to prepare our bodies for the alternating periods of sleep and wakefulness would be through the use of its connections with the hypothalamic preautonomic neurons to control the daily setting of the sympathetic-parasympathetic balance of autonomic inputs to these peripheral organs. Indeed, in a first series of viral tracing experiments, we were able to show a clear separation of the preautonomic neurons that control the sympathetic and parasympathetic branch of the ANS, up to the level of the second-order neurons in the hypothalamus (15, 16). Subsequently, we investigated whether within the biological clock one single group of neurons would be dedicated to the control of these sympathetic and parasympathetic preautonomic neurons or whether also within the SCN there is a clear separation of neurons controlling the sympathetic and parasympathetic branches of the ANS (20). Using a combination of double viral tracing and selective organ denervation, we were able to demonstrate that the segregation of presympathetic and pre-parasympathetic neurons already starts at the level of the SCN (Fig. 1Go). Clearly, this high level of differentiation puts the SCN in a unique position to balance the activity of both ANS branches according to the time of day.


Figure 1
View larger version (16K):
[in this window]
[in a new window]

  		FIG. 1. The SCN balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons. A, Schematic drawing of a sagittal section of the rat brain indicating the experimental setup used to examine the possible separation of sympathetic and parasympathetic preautonomic neurons in the hypothalamus. ß-Galactoside PRV (ßGAL-PRV) was injected into the sympathetic denervated liver, forcing the virus to infect the brain via the vagus nerve (red lines); simultaneously, the presympathetic neurons were labeled by an injection of green fluorescent protein (GFP)-PRV into the adrenal (green lines). After the labeling of the first-order neurons in the brainstem and spinal cord, this approach resulted in separate pre-parasympathetic and sympathetic neurons in the PVN (second order), followed by a similar separation of the third-order neurons in the SCN. Transverse sections of the hypothalamus in the region of the PVN (B) and SCN (C) show a perfect separation of pre-parasympathetic ßGAL-PRV (red) and pre-sympathetic GFP-PRV (green) labeled neurons.

 

   The SCN and the Metabolic Syndrome
Top
 Abstract
 Introduction
 SCN Outputs
 Balancing SCN Outputs
 The SCN and the...
Social Jetlag
 References
 
Obesity is characterized by excessive accumulation of triglycerides in adipose tissue. Accumulation of triglycerides in adipose tissue is determined by the net balance of fatty acid uptake and release being in favor of fat storage over fat mobilization. The rich innervation of adipose tissue by sympathetic fibers is well known, and activation of these fibers is associated with enhanced lipolysis (21). Until a few years ago, however, parasympathetic innervation of adipose tissue was thought to be nonexistent, and lipogenesis was thought to be merely controlled by hormones and the mass action of free fatty acids. In view of the importance of this balance between lipogenesis and lipolysis for the development of obesity, and the capability of the SCN to control the sympathetic/parasympathetic balance in other organs, we reinvestigated the existence of parasympathetic input to the adipose tissue to test the possibility of a SCN control of this lipogenesis/lipolysis balance through the ANS. Indeed, as previously reported by others (22), at a first instance, we too found little parasympathetic input to the white adipose tissue. However, upon combining the viral tracing technique with a prior selective denervation of the targeted fat pad, we found a pronounced labeling of the parasympathetic motor neurons in the brainstem (23). These observations provided the neuroanatomical substrate for earlier pharmacological observations in microdialysis studies in humans (24) and the more recent identification of functional acetylcholine receptors in rat adipocytes (25). In addition, our own functional studies provided clear evidence for the anabolic function of this parasympathetic innervation of adipose tissue. Euglycemic hyperinsulinemic clamp studies revealed more than 30% reduction in the insulin-mediated uptake of glucose and free fatty acids in adipose tissue as a result of a selective removal of its parasympathetic input. Moreover, without parasympathetic input, the activity of the catabolic enzyme hormone-sensitive lipase increased by 51% in the denervated adipose tissue (23). Additional follow-up studies using two different pseudorabies virus (PRV) tracers and selective denervation of the adipose tissue showed the presence of both sympathetic and parasympathetic adipose neurons in the hypothalamus, including the SCN (26). These results provide clear evidence that the SCN may use the ANS to enforce its day/night rhythms also upon the endocrine and metabolic functioning of the adipose tissue. Indeed, both fat deposition (by the key enzyme lipoprotein lipase) and fat mobilization (by hormone-sensitive lipase) show a clear daily rhythm in the white adipose tissue of both humans and laboratory animals (27, 28, 29, 30, 31). Plasma concentrations of the adipose tissue hormone leptin show a clear circadian rhythm as well (32), which is not controlled by circulating glucocorticoid levels, but which has disappeared after SCN lesions (Fig. 2Go) (33). In addition, the circulating plasma levels of a number of other adipocytokines (as well as their adipose mRNA levels) show clear day/night rhythms (34, 35, 36).


Figure 2
View larger version (18K):
[in this window]
[in a new window]

  		FIG. 2. Daily plasma leptin profiles in different experimental conditions. The daily plasma leptin profile of SCN-intact control animals ({circ}) is compared with that in SCN-lesioned animals (bullet), in adrenalectomized and corticosterone-treated animals ({triangleup}), and in animals on a regular feeding schedule ({blacksquare}). The results show a clear day/night rhythm in plasma leptin concentrations in intact animals that is abolished by SCN lesions, but not the removal of day/night rhythms in glucocorticoids or feeding behavior. Animals on the regular feeding schedule were adapted to a feeding schedule of one meal (3–4 g) every 4 h for more than 4 wk (33 ). All other groups were fed ad libitum. Asterisks indicate plasma leptin values significantly different (P < 0.01) from trough values between Zeitgeber time 0 and Zeitgeber time 6. Symbols indicate mean ± SEM. Zeitgeber time 0 and Zeitgeber time 12 are defined as the onset of the light and dark period, respectively.

 
Not all adipose tissue is equally harmful. Excessive intraabdominal fat is far worse than excessive sc fat, due to its much stronger association with the metabolic syndrome and type 2 diabetes (37). Therefore, we also investigated the question whether the central nervous system control of adipose tissue would be able to differentiate between different fat compartments. Using a combination of differently labeled (PRV) tracers injected into either an intraabdominal or a sc fat pad, and selective denervations, we were able to demonstrate that separate neurons are in charge of the different fat compartments (17, 23). Previously, this differential innervation of the different fat depots had already been demonstrated for adipose neurons in sympathetic ganglia (38), but our results show that this differential control is also valid for the parasympathetic input. Moreover, for both branches of the ANS, this differential control already starts at the level of the hypothalamus. At present, it is not clear yet to what extent this differential innervation by both branches of the ANS explains the functional differences between the different fat compartments (e.g. between visceral and sc fat). A nice series of recent experiments, however, clearly supports the functional significance of a neuroanatomical network for body fat distribution. It is well known that impaired estrogen signaling (either through a lack of estrogens or a lack of the estrogen receptor) promotes intraabdominal fat storage, both in rodents and humans (39, 40). Surprisingly, intraventricular administration of estrogen in estrogen-deficient female rodents is sufficient to prevent the intraabdominal accumulation of body fat (41), whereas specific silencing of the estrogen {alpha}-receptor in the ventromedial nucleus of the hypothalamus is sufficient to induce a shift of body fat from the sc to the abdominal compartment (42).


   Social Jetlag
Top
 Abstract
 Introduction
 SCN Outputs
 Balancing SCN Outputs
 The SCN and the...
 Social Jetlag
References
 
There is accumulating evidence for an intimate relation between circadian and metabolic cell systems (43, 44). In their recent reviews, Hastings et al. (45) and Foster and Wulff (46) clearly outlined how the misalignment of biological and social time may cause circadian desynchrony possibly resulting in chronic illnesses such as the metabolic syndrome and also cardiovascular and gastrointestinal diseases. Indeed, with the invention of the electric light bulb, the advent of jet travel and the expansion of shift work, the daily cycles of rest and wakefulness, and corresponding periods of fasting and eating, are no longer organized according to the presence of natural light. Using a simple questionnaire, Roenneberg and co-workers (47, 48) investigated the sleep/wake habits of more than 25,000 people and determined their chronotype. They concluded that not only shift workers but also more than half of the population lives with a body clock that is permanently out of phase with environmental time, a condition that they dubbed social jetlag (49). On the other hand, in a recent review, it was pointed out that in the past decades, many lifestyle changes have occurred that correlate with the increased prevalence of the metabolic syndrome (50). Interestingly, many of these lifestyle changes resulted in an attenuation of the rhythmic feedback signals as received by our biological clock in the preindustrial age, i.e. a diminished amplitude of the light/dark, warm/cold, active/inactive, sleep/wake, and satiety/hunger cycles. Therefore, we propose that in addition to the big two (increased physical activity and decreased intake of high-energy food), also a well-lighted and well-resonating clock may be helpful to withstand the increasing diabesity pressure of today’s 24/7 society.


   Footnotes
 
Disclosure Statement: The authors have nothing to disclose.

First Published Online September 27, 2007

Based on talk given at the "From Molecular Clocks to Human Health" session at the Sixth International Congress of Neuroendocrinology, Pittsburgh, PA, June 2006.

Abbreviations: ANS, Autonomic nervous system; PRV, pseudorabies virus; PVN, paraventricular nucleus; SCN, suprachiasmatic nuclei; VP, vasopressin.

Received June 13, 2007.

Accepted for publication August 16, 2007.


   References
Top
 Abstract
 Introduction
 SCN Outputs
 Balancing SCN Outputs
 The SCN and the...
 Social Jetlag
 References
 

  1. Reppert SM, Artman HG, Swaminathan S, Fisher DA 1981 Vasopressin exhibits a rhythmic daily pattern in cerebrospinal fluid but not in blood. Science 213:1256–1257[Free Full Text]
  2. Gillette MU, Reppert SM 1987 The hypothalamic suprachiasmatic nuclei: circadian patterns of vasopressin secretion and neuronal activity in vitro. Brain Res Bull 19:135–139[CrossRef][Medline]
  3. Buijs RM, Scheer FA, Kreier F, Yi C, Bos N, Goncharuk VD, Kalsbeek A 2006 Organization of circadian functions: interaction with the body. Prog Brain Res 153:341–360[Medline]
  4. Morin LP, Shivers KY, Blanchard JH, Muscat L 2006 Complex organization of mouse and rat suprachiasmatic nucleus. Neuroscience 137:1285–1297[CrossRef][Medline]
  5. Lehman MN, Silver R, Gladstone WR, Kahn RM, Gibson M, Bittman EL 1987 Circadian rhythmicity restored by neural transplant. Immunocytochemical characterization of the graft and its integration with the host brain. J Neurosci 7:1626–1638[Abstract]
  6. Meyer-Bernstein EL, Jetton AE, Matsumoto SI, Markuns JF, Lehman MN, Bittman EL 1999 Effects of suprachiasmatic transplants on circadian rhythms of neuroendocrine function in golden hamsters. Endocrinology 140:207–218[Abstract/Free Full Text]
  7. Guo H, Brewer JM, Champhekar A, Harris RB, Bittman EL 2005 Differential control of peripheral circadian rhythms by suprachiasmatic-dependent neural signals. Proc Natl Acad Sci USA 102:3111–3116[Abstract/Free Full Text]
  8. de la Iglesia HO, Meyer J, Schwartz WJ 2003 Lateralization of circadian pacemaker output: activation of left- and right-sided luteinizing hormone-releasing hormone neurons involves a neural rather than a humoral pathway. J Neurosci 23:7412–7414[Abstract/Free Full Text]
  9. Hoorneman EMD, Buijs RM 1982 Vasopressin fiber pathways in the rat brain following suprachiasmatic nucleus lesioning. Brain Res 243:235–241[CrossRef][Medline]
  10. Watts AG, Swanson LW 1987 Efferent projections of the suprachiasmatic nucleus. II. Studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat. J Comp Neurol 258:230–252[CrossRef][Medline]
  11. Hermes ML, Coderre EM, Buijs RM, Renaud LP 1996 GABA and glutamate mediate rapid neurotransmission from suprachiasmatic nucleus to hypothalamic paraventricular nucleus in the rat. J Physiol 496:749–757[Abstract/Free Full Text]
  12. Kalsbeek A, Buijs RM 2002 Output pathways of the mammalian suprachiasmatic nucleus: coding circadian time by transmitter selection and specific targeting. Cell Tissue Res 309:109–118[CrossRef][Medline]
  13. Buijs RM, Kalsbeek A 2001 Hypothalamic integration of central and peripheral clocks. Nat Neurosci Rev 2:521–526[CrossRef]
  14. Kalsbeek A, Palm IF, La Fleur SE, Scheer FA, Perreau-Lenz S, Ruiter M, Kreier F, Cailotto C, Buis RM 2006 SCN outputs and the hypothalamic balance of life. J Biol Rhythms 21:458–469[Abstract/Free Full Text]
  15. Kalsbeek A, La Fleur SE, Van Heijningen C, Buijs RM 2004 Suprachiasmatic GABAergic inputs to the paraventricular nucleus control plasma glucose concentrations in the rat via sympathetic innervation of the liver. J Neurosci 24:7604–7613[Abstract/Free Full Text]
  16. Buijs RM, Chun SJ, Niijima A, Romijn HJ, Nagai K 2001 Parasympathetic and sympathetic control of the pancreas: a role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake. J Comp Neurol 431:405–423[CrossRef][Medline]
  17. Kreier F, Kap YS, Mettenleiter T, Van Heijningen C, Van Der Vliet J, Kalsbeek A, Sauerwein H, Fliers E, Romijn JA, Buijs RM 2006 Tracing from fat tissue, liver, and pancreas: a neuroanatomical framework for the role of the brain in type2 diabetes. Endocrinology 147:1140–1147[Abstract/Free Full Text]
  18. Bartness TJ, Song CK, Demas GE 2001 SCN efferents to peripheral tissues: implications for biological rhythms. J Biol Rhythms 16:196–204[Abstract/Free Full Text]
  19. Pocai A, Obici S, Schwartz GJ, Rossetti L 2005 A brain-liver circuit regulates glucose homeostasis. Cell Metab 1:3–11[CrossRef]
  20. Buijs RM, la Fleur SE, Wortel J, Van Heijningen C, Zuiddam L, Mettenleiter TC, Kalsbeek A, Nagai K, Niijima A 2003 The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons. J Comp Neurol 464:36–48[CrossRef][Medline]
  21. Weiss B, Maickel RP 1968 Sympathetic nervous control of adipose tissue lipolysis. Int J Neuropharmacol 7:395–403[CrossRef][Medline]
  22. Bamshad M, Aoki VT, Adkison MG, Warren WS, Bartness TJ 1998 Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue. Am J Physiol 275:R291–R299
  23. Kreier F, Fliers E, Voshol PJ, Van Eden CG, Havekes LM, Kalsbeek A, Van Heijningen C, Sluiter AA, Mettenleiter TC, Romijn JA, Sauerwein H, Buijs RM 2002 Selective parasympathetic innervation of subcutaneous and intra-abdominal fat: functional implications. J Clin Invest 110:1243–1250[CrossRef][Medline]
  24. Andersson K, Arner P 1995 Cholinoceptor-mediated effects on glycerol output from human adipose tissue using in situ microdialysis. Br J Pharmacol 115:1155–1162[Medline]
  25. Liu RH, Mizuta M, Matsukura S 2004 The expression and functional role of nicotinic acetylcholine receptors in rat adipocytes. J Pharmacol Exp Ther 310:52–58[Abstract/Free Full Text]
  26. Kreier F 2005 Dual sympathetic and parasympathetic hypothalamic output to white adipose tissue. In: Autonomic nervous control of white adipose tissue, Chap. 4, Dissertation, University of Amsterdam
  27. Cornish S, Cawthorne MA 1978 Fatty acid synthesis in mice during the 24hr cycle and during meal-feeding. Horm Metab Res 10:286–290[Medline]
  28. Benavides A, Siches M, Llobera M 1998 Circadian rhythms of lipoprotein lipase and hepatic lipase activities in intermediate metabolism of adult rat. Am J Physiol 275:R811–R817
  29. Hagström-Toft E, Bolinder J, Ungerstedt U, Arner P 1997 A circadian rhythm in lipid mobilization which is altered in IDDM. Diabetologia 40:1070–1078[CrossRef][Medline]
  30. Bergö M, Olivecrona G, Olivecrona T 1996 Diurnal rhythms and effects of fasting and refeeding on rat adipose tissue lipoprotein lipase. Am J Physiol 271:E1092–E1097
  31. Hems DA, Rath EA, Verrinder TR 1975 Fatty acid synthesis in liver and adipose tissue of normal and genetically obese (ob/ob) mice during the 24-hour cycle. Biochem J 150:167–173[Medline]
  32. Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, Marco C, Caro JF 1996 Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 97:1344–1347[Medline]
  33. Kalsbeek A, Fliers E, Romijn JA, La Fleur SE, Wortel J, Bakker O, Endert E, Buijs RM 2001 The suprachiasmatic nucleus generates the diurnal changes in plasma leptin levels. Endocrinology 142:2677–2685[Abstract/Free Full Text]
  34. Gavrila A, Peng CK, Chan JL, Mietus JE, Goldberger AL, Mantzoros CS 2003 Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns. J Clin Endocrinol Metab 88:2838–2843[Abstract/Free Full Text]
  35. Rajala MW, Qi Y, Patel HR, Takahashi N, Banerjee R, Pajvani UB, Sinha MK, Gingerich RL, Scherer PE, Ahima RS 2004 Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes 53:1671–1679[Abstract/Free Full Text]
  36. Ando H, Yanagihara H, Hayashi Y, Obi Y, Tsuruoka S, Takamura T, Kaneko S, Fujimura A 2005 Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology 146:5631–5636[Abstract/Free Full Text]
  37. Depres JP, Lemieux I 2006 Abdominal obesity and metabolic syndrome. Nature 444:881–887[CrossRef][Medline]
  38. Youngstrom TG, Bartness TJ 1995 Catecholaminergic innervation of white adipose tissue in Siberian hamsters. Am J Physiol 268:R744–R751
  39. Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS 2000 Increased adipose tissue in male and female estrogen receptor-{alpha} knockout mice. Proc Natl Acad Sci USA 97:12729–12734[Abstract/Free Full Text]
  40. Mayes JS, Watson GH 2004 Direct effects of sex steroid hormones on adipose tissue and obesity. Obesity Rev 5:197–216[CrossRef]
  41. Clegg DJ, Brown LM, Woods SC, Benoit SC 2006 Gonadal hormones determine sensitivity to central leptin and insulin. Diabetes 55:978–987[Abstract/Free Full Text]
  42. Musatov S, Chen W, Pfaff DW, Mobbs CV, Yang XJ, Clegg DJ, Kaplitt MG, Ogawa S 2007 Silencing of estrogen receptor {alpha} in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. Proc Natl Acad Sci USA 104:2501–2506[Abstract/Free Full Text]
  43. Tu BP, McKnight SL 2006 Metabolic cycles as an underlying basis of biological oscillations. Nat Rev Mol Cell Biol 7:696–701[CrossRef][Medline]
  44. Kohsaka A, Bass J 2007 A sense of time: how molecular clocks organize metabolism. Trends Endocrinol Metab 18:4–11[CrossRef][Medline]
  45. Hastings MH, Reddy AB, Maywood ES 2003 A clockwork web: circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci 4:649–661[Medline]
  46. Foster RG, Wulff K 2005 The rhythm of rest and excess. Nat Rev Neurosci 6:407–414[CrossRef][Medline]
  47. Roenneberg T, Wirz-Justice A, Merrow M 2003 Life between clocks: daily temporal patterns of human chronotypes. J Biol Rhythms 18:80–90[Abstract/Free Full Text]
  48. Roenneberg T, Kuehnle T, Pramstaller PP, Ricken J, Havel M, Guth A, Merrow M 2004 A marker for the end of adolescence. Curr Biol 14:R1038–R1039
  49. Wittmann M, Dinich J, Merrow M, Roenneberg T 2006 Social jetlag: misalignment of biological and social time. Chronobiol Int 23:497–509[CrossRef][Medline]
  50. Keith SW, Redden DT, Katzmarzyk PT, Boggiano MM, Hanlon EC, Benca RM, Ruden D, Pietrobelli A, Barger JL, Fontaine KR, Wang C, Aronne LJ, Wright SM, Baskin M, Dhurandhar NV, Lijoi MC, Grilo CM, DeLuca M, Westfall AO, Allison DB 2006 Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obesity 30:1585–1594[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. C. Jensen, L. Bennet, S.-J. Guild, L. C. Booth, J. Stewart, and A. J. Gunn
The role of the neural sympathetic and parasympathetic systems in diurnal and sleep state-related cardiovascular rhythms in the late-gestation ovine fetus
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R998 - R1008.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. M. Novak
Neuromedin S and U
Endocrinology, July 1, 2009; 150(7): 2985 - 2987.
[Full Text] [PDF]

Home page
 J EndocrinolHome page
D. R Lemos, J. L Downs, M. N Raitiere, and H. F Urbanski
Photoperiodic modulation of adrenal gland function in the rhesus macaque: effect on 24-h plasma cortisol and dehydroepiandrosterone sulfate rhythms and adrenal gland gene expression
J. Endocrinol., May 1, 2009; 201(2): 275 - 285.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. N. Karatsoreos and R. Silver
Minireview: The Neuroendocrinology of the Suprachiasmatic Nucleus as a Conductor of Body Time in Mammals
Endocrinology, December 1, 2007; 148(12): 5640 - 5647.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kalsbeek, A.
Right arrow Articles by Buijs, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kalsbeek, A.
Right arrow Articles by Buijs, R. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals