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Article ; Online: Central angiotensin 1-7 triggers brown fat thermogenesis.

Evangelista, F S / Bartness, T J

2023 Volume 11, Issue 5, Page(s) e15621

Abstract: We tested the hypothesis that third ventricular (3V) injections of angiotensin 1-7 (Ang 1-7) increases thermogenesis in brown adipose tissue (BAT), and whether the Mas receptor mediates this response. First, in male Siberian hamsters (n = 18), we ... ...

Abstract	We tested the hypothesis that third ventricular (3V) injections of angiotensin 1-7 (Ang 1-7) increases thermogenesis in brown adipose tissue (BAT), and whether the Mas receptor mediates this response. First, in male Siberian hamsters (n = 18), we evaluated the effect of Ang 1-7 in the interscapular BAT (IBAT) temperature and, using selective Mas receptor antagonist A-779, the role of Mas receptor in this response. Each animal received 3V injections (200 nL), with 48 h intervals: saline; Ang 1-7 (0.03, 0.3, 3, and 30 nmol); A-779 (3 nmol); and Ang 1-7 (0.3 nmol) + A-779 (3 nmol). IBAT temperature increased after 0.3 nmol Ang 1-7 compared with Ang 1-7 + A-779 at 20, 30, and 60 min. Also, 0.3 nmol Ang 1-7 increased IBAT temperature at 10 and 20 min, and decreased at 60 min compared with pretreatment. IBAT temperature decreased after A-779 at 60 min and after Ang 1-7 + A-779 at 30 and 60 min compared with the respective pretreatment. A-779 and Ang 1-7 + A-779 decreased core temperature at 60 min compared with 10 min. Then, we evaluated blood and tissue Ang 1-7 levels, and the expression of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in IBAT. Male Siberian hamsters (n = 36) were killed 10 min after one of the injections. No changes were observed in blood glucose, serum and IBAT Ang 1-7 levels, and ATGL. Ang 1-7 (0.3 nmol) increased p-HSL expression compared with A-779 and increased p-HSL/HSL ration compared with other injections. Ang 1-7 and Mas receptor immunoreactive cells were found in brain regions that coincide with the sympathetic nerves outflow to BAT. In conclusion, 3V injection of Ang 1-7 induced thermogenesis in IBAT in a Mas receptor-dependent manner.
MeSH term(s)	Cricetinae ; Animals ; Male ; Phodopus ; Adipose Tissue, Brown/metabolism ; Thermogenesis/physiology ; Sympathetic Nervous System/physiology
Chemical Substances	angiotensin I (1-7) (IJ3FUK8MOF)
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15621
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Article ; Online: Editorial on Ding et al. 'Adipose afferent reflex responses to insulin is mediated by melanocortin 4 type receptors in the paraventricular nucleus in insulin resistance rats'.

Bartness, T J / Garretson, J T

Acta physiologica (Oxford, England)

2015 Volume 214, Issue 4, Page(s) 432–435

MeSH term(s)	Adipose Tissue, White/metabolism ; Animals ; Insulin Resistance/physiology ; Male ; Paraventricular Hypothalamic Nucleus/metabolism ; Receptor, Melanocortin, Type 4/metabolism ; Sympathetic Nervous System/physiology
Chemical Substances	Receptor, Melanocortin, Type 4
Language	English
Publishing date	2015-08
Publishing country	England
Document type	Comment ; Editorial
ZDB-ID	2218636-0
ISSN	1748-1716 ; 1748-1708
ISSN (online)	1748-1716
ISSN	1748-1708
DOI	10.1111/apha.12541
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Article ; Online: Sensory denervation of inguinal white fat modifies sympathetic outflow to white and brown fat in Siberian hamsters.

Nguyen, Ngoc Ly T / Xue, Bingzhong / Bartness, Timothy J

Physiology & behavior

2018 Volume 190, Page(s) 28–33

Abstract: White adipose tissue (WAT) and brown adipose tissue (BAT) have sympathetic nervous system (SNS) and sensory innervations. Previous studies from our laboratory revealed central neuroanatomical evidence of WAT sensory and BAT SNS crosstalk with double ... ...

Abstract	White adipose tissue (WAT) and brown adipose tissue (BAT) have sympathetic nervous system (SNS) and sensory innervations. Previous studies from our laboratory revealed central neuroanatomical evidence of WAT sensory and BAT SNS crosstalk with double labeling of inguinal WAT (IWAT) sensory and interscapular BAT (IBAT) SNS neurons. We previously demonstrated that WAT lipolysis increases IBAT temperature, but this effect is absent when IWAT afferents are surgically denervated, which severs both sensory and SNS nerves. It is possible that WAT sensory feedback can regulate SNS drive to itself and other WAT and BAT depots, and thus contribute to the existence of differential SNS outflow to fat during different energy challenges. Here we selectively denervated IWAT sensory nerves in Siberian hamsters using capsaicin and measured norepinephrine turnover (NETO) i.e., SNS drive to WAT and BAT depots, IBAT uncoupling protein 1 (UCP1) expression, body mass, fat mass, blood glucose, and food consumed after a 24-h cold exposure. IWAT sensory denervation decreased both IWAT and IBAT NETO and IBAT UCP1 expression. IWAT sensory denervation, however, increased mesenteric WAT (MWAT) NETO after the 24-h cold exposure and did not modify epididymal WAT (EWAT) and retroperitoneal WAT (RWAT) NETO compared with respective controls. Body mass, fat mass, blood glucose, and food consumed were unchanged across groups. RWAT and EWAT mass decreased in capsaicin-injected hamsters, but did not in the vehicle hamsters. These results functionally demonstrate the existence of IWAT sensory and IBAT SNS crosstalk and that a disruption in this sensory-SNS feedback mechanism modifies SNS drive to IWAT, IBAT, and MWAT, but not EWAT and RWAT.
MeSH term(s)	Adipose Tissue, Brown/innervation ; Adipose Tissue, White/innervation ; Animals ; Blood Glucose/metabolism ; Body Mass Index ; Capsaicin ; Cricetinae ; Denervation ; Eating/physiology ; Intra-Abdominal Fat/innervation ; Male ; Norepinephrine/metabolism ; Peripheral Nerves/drug effects ; Phodopus ; Sympathetic Nervous System/physiology ; Uncoupling Protein 1/biosynthesis
Chemical Substances	Blood Glucose ; Uncoupling Protein 1 ; Capsaicin (S07O44R1ZM) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2018-02-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2018.02.019
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Article: Neural control of white, beige and brown adipocytes.

Bartness, T J / Ryu, V

International journal of obesity supplements

2015 Volume 5, Issue Suppl 1, Page(s) S35–9

Abstract: Reports of brown-like adipocytes in traditionally white adipose tissue (WAT) depots occurred ~30 years ago, but interest in white adipocyte 'browning' only has gained attention more recently. We integrate some of what is known about the sympathetic ... ...

Abstract	Reports of brown-like adipocytes in traditionally white adipose tissue (WAT) depots occurred ~30 years ago, but interest in white adipocyte 'browning' only has gained attention more recently. We integrate some of what is known about the sympathetic nervous system (SNS) innervation of WAT and brown adipose tissue (BAT) with the few studies focusing on the sympathetic innervation of the so-called 'brite' or 'beige' adipocytes that appear when WAT sympathetic drive increases (for example, cold exposure and food deprivation). Only one brain site, the dorsomedial hypothalamic nucleus (DMH), selectively browns some (inguinal WAT (IWAT) and dorsomedial subcutaneous WAT), but not all WAT depots and only when DMH neuropeptide Y gene expression is knocked down, a browning effect is mediated by WAT SNS innervation. Other studies show that WAT sympathetic fiber density is correlated with the number of brown-like adipocytes (multilocular lipid droplets, uncoupling protein-1 immunoreactivity) at both warm and cold ambient temperatures. WAT and BAT have sensory innervation, the latter important for acute BAT cold-induced temperature increases, therefore suggesting the possible importance of sensory neural feedback from brite/beige cells for heat production. Only one report shows browned WAT capable of producing heat in vivo. Collectively, increases in WAT sympathetic drive and the phenotype of these stimulated adipocytes seems critical for the production of new and/or transdifferentiation of white to brite/beige adipocytes. Selective harnessing of WAT SNS drive to produce browning or selective browning independent of the SNS to counter increases in adiposity by increasing expenditure appears to be extremely challenging.
Language	English
Publishing date	2015-08-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2629968-9
ISSN	2046-2174 ; 2046-2166
ISSN (online)	2046-2174
ISSN	2046-2166
DOI	10.1038/ijosup.2015.9
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Article ; Online: Dynamic modification of hoarding in response to hoard size manipulation.

Garretson, John T / Bartness, Timothy J

Physiology & behavior

2014 Volume 127, Page(s) 8–12

Abstract: Food hoarding is an evolutionary adaptation whereby animals store food for later consumption when food is limited or when predation risk while foraging is high. It also occurs as part of normal appetitive behavior by humans and non-human animals when ... ...

Abstract	Food hoarding is an evolutionary adaptation whereby animals store food for later consumption when food is limited or when predation risk while foraging is high. It also occurs as part of normal appetitive behavior by humans and non-human animals when they are hungry. Contrary to popular belief, humans do not overeat after food restriction/fasting, rather they increase food hoarding, as do hamster species, but not in laboratory rats or mice. Thus, this aspect of human appetitive behavior is better modeled by hamsters than laboratory rats and mice. Here we tested whether male Siberian hamsters (Phodopus sungorus) modify their daily food hoard size under ad libitum-feeding and after food deprivation when we artificially increased or removed their food hoard. When the food hoard was completely removed, hamsters hoarded more food the next day than did animals where the hoard was surreptitiously increased. Hamsters that had alternating daily hoard increases/decreases rapidly adjusted their food hoarding inversely proportional to food hoard size. Similarly, after 48h of food deprivation, a stimulus that initiates high levels of food hoarding upon refeeding in this species, hamsters with artificially increased food hoard size hoarded significantly less than did hamsters where we left the hoard unaltered additionally suggesting that food hoard size directly affects food hoarding. Collectively, as we previously found when the caloric value of the food offered was increased or decreased, food hoard size is in some sense 'regulated' and not simply a reflexive response triggered by inter-meal hunger or food deprivation.
MeSH term(s)	Animals ; Appetitive Behavior ; Feeding Behavior ; Food ; Food Deprivation ; Male ; Phodopus ; Time Factors
Language	English
Publishing date	2014-01-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2013.12.008
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Article ; Online: Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses.

Vaughan, Cheryl H / Bartness, Timothy J

American journal of physiology. Regulatory, integrative and comparative physiology

2012 Volume 302, Issue 9, Page(s) R1049–58

Abstract: ... core (T(c)) and IBAT (T(IBAT)) temperature responses. CGRP content was significantly decreased ... in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. T(IBAT) and T(c) were ...

Abstract	Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (T(c)) and IBAT (T(IBAT)) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. T(IBAT) and T(c) were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure.
MeSH term(s)	Adipose Tissue, Brown/innervation ; Adipose Tissue, Brown/physiology ; Adrenergic Fibers/physiology ; Afferent Pathways/anatomy & histology ; Afferent Pathways/physiology ; Animals ; Cricetinae ; Denervation ; Herpesvirus 1, Human ; Sympathectomy ; Sympathetic Nervous System/anatomy & histology ; Sympathetic Nervous System/physiology ; Sympathetic Nervous System/virology ; Thermogenesis/physiology ; Thermosensing/physiology
Language	English
Publishing date	2012-02-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00640.2011
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Article: North American Association for the Study of Obesity annual meeting.

Bartness, T J

IDrugs : the investigational drugs journal

2001 Volume 4, Issue 1, Page(s) 41–43

Abstract: The annual meeting of the North American Association for the Study of Obesity was held in Long Beach, CA, USA with approximately 1500 attendees, including basic and clinical obesity/food intake researchers and local and regional physicians. The meeting ... ...

Abstract	The annual meeting of the North American Association for the Study of Obesity was held in Long Beach, CA, USA with approximately 1500 attendees, including basic and clinical obesity/food intake researchers and local and regional physicians. The meeting highlighted a clear trend toward pharmacological approaches directed at the brain control of obesity/food intake/energy expenditure as well as combinations of therapies, eg, drug and dietary, two drugs, drug and behavioral change. The magnitude of the body weight losses in the human studies was typically 5 to 15% of starting weight, which was recognized as unsatisfactory. Examples of new developments included attempts to block receptors of accepted neuropeptides involved in food intake and energy expenditure, such as the neuropeptide Y (NPY) 5 receptor, documentation of the ability of current drugs used to treat other disorders that also decrease body weight/food intake, such as the antidepressant drug bupropion SR and the anti-epileptic agent topiramate, as well as development of new peptide receptor agonists, such as A-200, a modified human recombinant leptin preparation. Recognition of dietary supplements and over-the-counter medications as potential obesity promoting triggers, such as melatonin were also presented.
Language	English
Publishing date	2001-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2086568-5
ISSN	2040-3410 ; 1369-7056
ISSN (online)	2040-3410
ISSN	1369-7056
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Article ; Online: Central sympathetic innervations to visceral and subcutaneous white adipose tissue.

Nguyen, Ngoc Ly T / Randall, Jessica / Banfield, Bruce W / Bartness, Timothy J

American journal of physiology. Regulatory, integrative and comparative physiology

2014 Volume 306, Issue 6, Page(s) R375–86

Abstract: There is a link between visceral white adipose tissue (WAT) and the metabolic syndrome in humans, with health improvements produced with small visceral WAT reduction. By contrast, subcutaneous WAT provides a site for lipid storage that is rather ... ...

Abstract	There is a link between visceral white adipose tissue (WAT) and the metabolic syndrome in humans, with health improvements produced with small visceral WAT reduction. By contrast, subcutaneous WAT provides a site for lipid storage that is rather innocuous relative to ectopic lipid storage in muscle or liver. The sympathetic nervous system (SNS) is the principal initiator for lipolysis in WAT by mammals. Nothing is known, however, about the central origins of the SNS circuitry innervating the only true visceral WAT in rodents, mesenteric WAT (MWAT), which drains into the hepatic portal vein. We tested whether the central sympathetic circuits to subcutaneous [inguinal WAT (IWAT)] and visceral WAT (MWAT) are separate or shared and whether they possess differential sympathetic drives with food deprivation in Siberian hamsters. Using two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer within the same hamsters, we found some overlap (∼20-55% doubly infected neurons) between the two circuitries across the neural axis with lesser overlap proximal to the depots (spinal cord and sympathetic chain) and with more neurons involved in the innervation of IWAT than MWAT in some brain regions. Food deprivation triggered a greater sympathetic drive to subcutaneous (IWAT) than visceral (MWAT) depots. Collectively, we demonstrated both shared and separate populations of brain, spinal cord, and sympathetic chain neurons ultimately project to a subcutaneous WAT depot (IWAT) and the only visceral WAT depot in rodents (MWAT). In addition, the lipolytic stimulus of food deprivation only increased SNS drive to subcutaneous fat (IWAT).
MeSH term(s)	Adipose Tissue, White/innervation ; Adipose Tissue, White/metabolism ; Adrenergic Fibers/physiology ; Animals ; Central Nervous System/cytology ; Central Nervous System/metabolism ; Cricetinae ; Food Deprivation/physiology ; Ganglia, Sympathetic/cytology ; Ganglia, Sympathetic/metabolism ; Herpesvirus 1, Suid ; Intra-Abdominal Fat/innervation ; Intra-Abdominal Fat/metabolism ; Lipolysis/physiology ; Male ; Neuronal Tract-Tracers ; Phodopus ; Subcutaneous Fat/innervation ; Subcutaneous Fat/metabolism
Chemical Substances	Neuronal Tract-Tracers
Language	English
Publishing date	2014-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00552.2013
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Article: Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis.

Garretson, John T / Szymanski, Laura A / Schwartz, Gary J / Xue, Bingzhong / Ryu, Vitaly / Bartness, Timothy J

Molecular metabolism

2016 Volume 5, Issue 8, Page(s) 626–634

Abstract: Objective: Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose ...

Abstract	Objective: Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve fibers that network to metabolic brain areas; moreover, activation of these afferents is reported to increase sympathetic nervous system outflow. However, the endogenous stimuli sufficient to drive WAT afferents during metabolic challenges as well as their functional relation to BAT thermogenesis remain unknown. Method: We tested if local WAT lipolysis directly activates WAT afferent nerves, and then assessed whether this WAT sensory signal affected BAT thermogenesis in Siberian hamsters (Phodopus sungorus). Results: 2-deoxyglucose, a sympathetic nervous system stimulant, caused β-adrenergic receptor dependent increases in inguinal WAT (IWAT) afferent neurophysiological activity. In addition, direct IWAT injections of the β3-AR agonist CL316,243 dose-dependently increased: 1) phosphorylation of IWAT hormone sensitive lipase, an indicator of SNS-stimulated lipolysis, 2) expression of the neuronal activation marker c-Fos in dorsal root ganglion neurons receiving sensory input from IWAT, and 3) IWAT afferent neurophysiological activity, an increase blocked by antilipolytic agent 3,5-dimethylpyrazole. Finally, we demonstrated that IWAT afferent activation by lipolysis triggers interscapular BAT thermogenesis through a neural link between these two tissues. Conclusions: These data suggest IWAT lipolysis activates local IWAT afferents triggering a neural circuit from WAT to BAT that acutely induces BAT thermogenesis.
Language	English
Publishing date	2016-08
Publishing country	Germany
Document type	Journal Article
ISSN	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2016.06.013
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Article ; Online: Separate and shared sympathetic outflow to white and brown fat coordinately regulates thermoregulation and beige adipocyte recruitment.

Nguyen, Ngoc Ly T / Barr, Candace L / Ryu, Vitaly / Cao, Qiang / Xue, Bingzhong / Bartness, Timothy J

American journal of physiology. Regulatory, integrative and comparative physiology

2016 Volume 312, Issue 1, Page(s) R132–R145

Abstract: White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their ... ...

Abstract	White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their function. We injected two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer, with unique fluorescent reporters into interscapular BAT (IBAT) and inguinal WAT (IWAT) of the same Siberian hamsters to define SNS pathways to both. To test the functional importance of SNS coordinated control of BAT and WAT, we exposed hamsters with denervated SNS nerves to IBAT to 4°C for 16-24 h and measured core and fat temperatures and norepinephrine turnover (NETO) and uncoupling protein 1 (UCP1) expression in fat tissues. Overall, there were more SNS neurons innervating IBAT than IWAT across the neuroaxis. However, there was a greater percentage of singly labeled IWAT neurons in midbrain reticular nuclei than singly labeled IBAT neurons. The hindbrain had ~30-40% of doubly labeled neurons while the forebrain had ~25% suggesting shared SNS circuitry to BAT and WAT across the brain. The raphe nucleus, a key region in thermoregulation, had ~40% doubly labeled neurons. Hamsters with IBAT SNS denervation maintained core body temperature during acute cold challenge and had increased beige adipocyte formation in IWAT. They also had increased IWAT NETO, temperature, and UCP1 expression compared with intact hamsters. These data provide strong neuroanatomical and functional evidence of WAT and BAT SNS cross talk for thermoregulation and beige adipocyte formation.
MeSH term(s)	Adipocytes/physiology ; Adipocytes, Beige/cytology ; Adipocytes, Beige/physiology ; Adipose Tissue, Brown/cytology ; Adipose Tissue, Brown/innervation ; Adipose Tissue, Brown/physiology ; Adipose Tissue, White/cytology ; Adipose Tissue, White/innervation ; Adipose Tissue, White/physiology ; Animals ; Body Temperature Regulation/physiology ; Cricetinae ; Feedback, Physiological/physiology ; Male ; Phodopus ; Sympathetic Nervous System/physiology ; Thermotolerance/physiology
Language	English
Publishing date	2016-11-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00344.2016
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