Hepatic portal injection of glucose elevates efferent sympathetic discharges of interscapular brown adipose tissue

doi:10.1016/0014-4886(88)90057-X

Experimental Neurology

Volume 101, Issue 3, September 1988, Pages 464-469

https://doi.org/10.1016/0014-4886(88)90057-X Get rights and content

Abstract

Efferent sympathetic discharges of interscapular brown adipose tissue were recorded after three different concentrations of glucose (138, 277, and 416 mM) and 154 mM NaCl were injected into the portal vein or into the right jugular vein. When injected into the portal vein there was a significant increase in the discharge in response to both concentrations of glucose (277 and 416 mM), whereas only 416 mM glucose solution could cause an increase in the discharge when injected into the right jugular vein. There was no appreciable change in the discharge following the NaCl injections into the portal and jugular veins, and the portal glucose responses in the discharge were abolished by transection of the hepatic branch of the vagus nerve. Since stimulated sympathetic activity has been shown to elevate thermogenesis of the adipose tissue, these findings suggest that vagal glucose signals derived from the portal vein may be involved in the regulation of heat production of this tissue.

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Cited by (12)

Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: Insights from mathematical modeling and meta-analysis
2020, Pharmacology and Therapeutics
Citation Excerpt :
Yet, there are many other reflexes that we do not understand, and some thermoregulatory reflexes that are triggered by nonthermal stimuli belong to this group. For example, skin vasoconstriction is affected by colorectal distension (Laird, Carrive, & Waite, 2006), while nonshivering thermogenesis is modulated by gastric stretching (Petervari, Garami, Pakai, & Szekely, 2005), the level of intraportal glucose (Sakaguchi & Yamazaki, 1988), and the osmolarity of the content in different parts of the gastrointestinal tract (Boschmann et al., 2007; Osaka, Kobayashi, & Inoue, 2002). All of the abovementioned reflexes seem illogical – but only until we study them, find the conditions under which they are expressed, or just start thinking about them.
Antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (T_b) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and heat. First-generation (polymodal) TRPV1 antagonists potently block all three TRPV1 activation modes. Second-generation (mode-selective) TRPV1 antagonists potently block channel activation by CAP, but exert different effects (e.g., potentiation, no effect, or low-potency inhibition) in the proton mode, heat mode, or both. Based on our earlier studies in rats, only one mode of TRPV1 activation – by protons – is involved in thermoregulatory responses to TRPV1 antagonists. In rats, compounds that potently block, potentiate, or have no effect on proton activation cause hyperthermia, hypothermia, or no effect on T_b, respectively. A T_b response occurs when a TRPV1 antagonist blocks (in case of hyperthermia) or potentiates (hypothermia) the tonic TRPV1 activation by protons somewhere in the trunk, perhaps in muscles, and – via the acido-antithermogenic and acido-antivasoconstrictor reflexes – modulates thermogenesis and skin vasoconstriction. In this work, we used a mathematical model to analyze T_b data from human clinical trials of TRPV1 antagonists. The analysis suggests that, in humans, the hyperthermic effect depends on the antagonist’s potency to block TRPV1 activation not only by protons, but also by heat, while the CAP activation mode is uninvolved. Whereas in rats TRPV1 drives thermoeffectors by mediating pH signals from the trunk, but not T_b signals, our analysis suggests that TRPV1 mediates both pH and thermal signals driving thermoregulation in humans. Hence, in humans (but not in rats), TRPV1 is likely to serve as a thermosensor of the thermoregulation system. We also conducted a meta-analysis of T_b data from human trials and found that polymodal TRPV1 antagonists (ABT-102, AZD1386, and V116517) increase T_b, whereas the mode-selective blocker NEO6860 does not. Several strategies of harnessing the thermoregulatory effects of TRPV1 antagonists in humans are discussed.
The thermoregulation system and how it works
2018, Handbook of Clinical Neurology
Citation Excerpt :
What he means is that there are numerous reflexes in the body that adjust a physiologic variable based on the information about a different, sometimes seemingly unrelated, variable. Such reflexes include changes in BAT thermogenesis caused by stomach distension (Pétervári et al., 2005), intraportal glucose (Sakaguchi and Yamazaki, 1988), or intraduodenal hypertonic saline (Osaka et al., 2002). Another example is the skin vasoconstrictor response to colorectal distension (Laird et al., 2006).
Heat exchange processes between the body and the environment are introduced. The definition of the thermoneutral zone as the ambient temperature range within which body temperature (T_b) regulation is achieved only by nonevaporative processes is explained. Thermoreceptors, thermoregulatory effectors (both physiologic and behavioral), and neural pathways and T_b signals that connect receptors and effectors into a thermoregulation system are reviewed. A classification of thermoeffectors is proposed. A consensus concept is presented, according to which the thermoregulation system is organized as a dynamic federation of independent thermoeffector loops. While the activity of each effector is driven by a unique combination of deep (core) and superficial (shell) T_bs, the regulated variable of the system can be viewed as a spatially distributed T_b with a heavily represented core and a lightly represented shell. Core T_b is the main feedback; it is always negative. Shell T_bs (mostly of the hairy skin) represent the auxiliary feedback, which can be negative or positive, and which decreases the system's response time and load error. Signals from the glabrous (nonhairy) skin about the temperature of objects in the environment serve as feedforward signals for various behaviors. Physiologic effectors do not use feedforward signals. The system interacts with other homeostatic systems by “meshing” with their loops. Coordination between different thermoeffectors is achieved through the common controlled variable, T_b. The term balance point (not set point) is used for a regulated level of T_b. The term interthreshold zone is used for a T_b range in which no effectors are activated. Thermoregulatory states are classified, based on whether: T_b is increased (hyperthermia) or decreased (hypothermia); the interthreshold zone is narrow (homeothermic type of regulation) or wide (poikilothermic type); and the balance point is increased (fever) or decreased (anapyrexia). During fever, thermoregulation can be either homeothermic or poikilothermic; anapyrexia is always a poikilothermic state. The biologic significance of poikilothermic states is discussed. As an example of practical applications of the concept presented, thermopharmacology is reviewed. Thermopharmacology uses drugs to modulate specific temperature signals at the level of a thermoreceptor (transient receptor potential channel).
A neurophysiological evidence of capsaicin-sensitive nerve components innervating interscapular brown adipose tissue
2005, Autonomic Neuroscience: Basic and Clinical
Neurophysiological basis for the heterogeneity of the nerve components in the brown adipose tissue (BAT) was examined in this experiment. Efferent nerve signals were recorded from the central cut end of the small nerve filament dissected from the nerve fibers innervating the interscapular BAT (IBAT). By focusing on qualitative aspects of observed compound action potentials (spikes), we found two distinctive types of spikes exhibited by the intercostal nerves innervating IBAT. The spikes mainly appeared upon sympathetic stimulations (cold stimulation and glucose administration) were characterized by low amplitude with relatively short duration (small spike) and their sensitivity to the ganglion blocker, hexamethonium (C6). On the other hand, the spikes seen throughout the experiments were characterized by high amplitude with long duration (large spike) and their insensitivity to C6. Since BAT is activated by cold and feeding via sympathetic nervous system, the small spikes seemed to be exhibited by sympathetic fibers. On the other hand, appearance of the large C6-insensitive spikes was strongly attenuated in capsaicin-desensitized rats. Even though the functional link between IBAT and C6 insensitive fibers remains unanswered, our results suggest that IBAT is under control of various nerve types including capsaicin-sensitive fibers in addition to the control of sympathetic nervous system.
Postalimentary hyperthermia: A role for gastrointestinal but not for caloric signals
2001, Journal of Thermal Biology
(1) Fasting causes suppression of resting body temperature (T_c) and metabolic rate (MR) in rats. (2) Re-feeding with conventional chow or saccharine-sweetened CaCO₃ elevates MR and T_c of fasting rats. It is not the composition, but the volume of ingested substance that is important. (3) MR- and T_c-elevations have different dynamics following injections of calorie-rich or -free substances through an intragastric cannula. (4) Intravenous infusions of 40% glucose or 20% fat emulsion do not influence MR and T_c. (5) Gastrointestinal, rather than caloric, signals determine the postalimentary hyperthermia.
The vagus nerve in thermoregulation and energy metabolism
2000, Autonomic Neuroscience: Basic and Clinical
The vagus nerve may indirectly influence thermoregulation by modulation of energy balance: its afferent fibers convey signals that represent information on feeding state, resulting in either depression or stimulation of metabolic processes. A regulated metabolic depression can be detected in the background of fasting-induced hypometabolism and hypothermia. In its development (besides humoral signals) vagally transmitted neural signals of gastrointestinal and hepatoportal origin are important. These signals are related to hunger, to decrease of mechanical/chemical stimuli from the gut, to decline of blood glucose; they alter discharge rates of vagal afferents and activity of the nucleus of the solitary tract, eliciting inhibition of metabolic rate and enhancement of food intake. In this hunger-related metabolic inhibition the nucleus of the solitary tract is in interaction with hypothalamic nuclei, that contribute to neuropeptide changes characterized by high neuropeptide Y activity (with energy-conserving type of regulation) and depressed cholecystokinin and corticotropin releasing hormone activities (with depressed energy-expenditure). In postalimentary states the hypermetabolism and hyperthermia are due to opposite changes in metabolic regulation. Satiety-related stimulatory signals of abdominal origin, transmitted via hepatic vagal afferents to the nucleus of the solitary tract, contribute to enhancement of sympathetic activity and stress-responsiveness, leading to hypermetabolism and hyperthermia. Depressed neuropeptide Y release and enhanced cholecystokinin and corticotropin releasing hormone activities participate in the central regulatory changes, and in the high energy-expenditure. The biological role of these vagal functions is not directly the regulation of body temperature, rather the regulation of energy balance and energy content in the body.
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¹: The authors are greatly indebted to Mr. S. Wakui and Mr. K. Kunihara for their assistance.

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Research noteHepatic portal injection of glucose elevates efferent sympathetic discharges of interscapular brown adipose tissue

Abstract

Brain Res. Bull.

Activity of single neurons in the hypothalamic feeding centers: Effect of glucose

Am. J. Physiol.

Afferent impulse discharges from glucoreceptors in the liver of the guinea pig

Ann. N.Y. Acad. Sci.

Effect of glucose and other hexoses on efferent discharges of brown adipose tissue nerves

Am. J. Physiol.

Role of ventromedial hypothalamus on sympathetic efferents of brown adipose tissue

Am. J. Physiol.

Behavior of hypothalamic unit activity during electrophoretic application of drugs

Ann. N.Y. Acad. Sci.

Research note
Hepatic portal injection of glucose elevates efferent sympathetic discharges of interscapular brown adipose tissue