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Deep Brain Stimulation of the Paraventricular Hypothalamus Activates Brown Adipose Tissue Sympathetic Nerve Activity: A Foundation for a Therapeutic Approach to Obesity
Author(s) -
Madden Christopher J,
Burchiel Kim,
Morrison Shaun F
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.559.5
Subject(s) - brown adipose tissue , stimulation , endocrinology , thermogenesis , medicine , hypothalamus , bicuculline , stimulus (psychology) , midbrain , biology , neuroscience , adipose tissue , central nervous system , antagonist , psychology , receptor , psychotherapist
Obesity is a major epidemic with enormous societal costs. Recently, surgical approaches to the treatment of obesity have become more common. Since the rediscovery of brown adipose tissue (BAT) in adult humans and the demonstration of the inverse correlation between BAT activation and obesity, BAT activation has emerged as a target for weight reduction. The main goal of this study was to demonstrate the “proof of concept” that electrical stimulation of hypothalamic sites could activate sympathetic outflow to BAT. In addition, these studies investigated optimal stimulus parameters and potential mechanisms underlying electrical stimulation‐induced increases in BAT sympathetic nerve activity (SNA). In urethane/chloralose anesthetized rats, maintained electrical stimulation (0.1mA, 0.1ms pulses, 100Hz trains for 5 sec periods with 50% duty cycle) of the paraventricular hypothalamus (PVH) elicited a biphasic response in BAT SNA. Initially, PVH stimulation inhibited BAT SNA, but this was followed by brief activations of BAT SNA during the off cycle between stimulus trains. After several minutes, PVH stimulation caused large activations of BAT SNA that occurred during both the on and off cycles, and these increased BAT temperature by 0.5–2.0 °C. These increases in BAT SNA and BAT thermogenesis were sustained for at least one hour of PVH stimulation. Nanoinjection of the GABAA antagonist, bicuculline, in the PVH prevented the stimulation‐evoked increases in BAT SNA and BAT thermogenesis. Thus, local release of GABA during PVH stimulation is necessary for the stimulus‐evoked activation of BAT SNA and increases in BAT metabolism. These data serve as a foundation for a potential approach to increasing metabolism in BAT for the treatment of obesity. Support or Funding Information NIH NCATS UL1‐TR000128 (CJM) and R01‐NS091066 (SFM) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .