Universität zu Köln

Bozadjieva-Kramer, Nadejda, Ross, Rachel A., Johnson, David Q., Fenselau, Henning, Haggerty, David L., Atwood, Brady ORCID: 0000-0002-7441-2724, Lowell, Bradford and Flak, Jonathan N. (2021). The Role of Mediobasal Hypothalamic PACAP in the Control of Body Weight and Metabolism. Endocrinology, 162 (4). WASHINGTON: ENDOCRINE SOC. ISSN 1945-7170

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Abstract

Body energy homeostasis results from balancing energy intake and energy expenditure. Central nervous system administration of pituitary adenylate cyclase activating polypeptide (PACAP) dramatically alters metabolic function, but the physiologic mechanism of this neuropeptide remains poorly defined. PACAP is expressed in the mediobasal hypothalamus (MBH), a brain area essential for energy balance. Ventromedial hypothalamic nucleus (VMN) neurons contain, by far, the largest and most dense population of PACAP in the medial hypothalamus.This region is involved in coordinating the sympathetic nervous system in response to metabolic cues in order to re-establish energy homeostasis. Additionally, the metabolic cue of leptin signaling in the VMN regulates PACAP expression. We hypothesized that PACAP may play a role in the various effector systems of energy homeostasis, and tested its role by using VMN-directed, but MBH encompassing, adeno-associated virus (AAV(Cre)) injections to ablate Adcyapl (gene coding for PACAP) in mice (Adcyap1(MBH)KO mice). Adcyap1(MBH)KO mice rapidly gained body weight and adiposity, becoming hyperinsulinemic and hyperglycemic. Adcyap1(MBH)KO mice exhibited decreased oxygen consumption (VO2), without changes in activity. These effects appear to be due at least in part to brown adipose tissue (BAT) dysfunction, and we show that PACAP-expressing cells in the MBH can stimulate BAT thermogenesis.While we observed disruption of glucose clearance during hyperinsulinemic/euglycemic clamp studies in obese Adcyap1(MBH)KO mice, these parameters were normal prior to the onset of obesity. Thus, MBH PACAP plays important roles in the regulation of metabolic rate and energy balance through multiple effector systems on multiple time scales, which highlight the diverse set of functions for PACAP in overall energy homeostasis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bozadjieva-Kramer, Nadejda UNSPECIFIED UNSPECIFIED UNSPECIFIED Ross, Rachel A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Johnson, David Q. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fenselau, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Haggerty, David L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Atwood, Brady UNSPECIFIED orcid.org/0000-0002-7441-2724 UNSPECIFIED Lowell, Bradford UNSPECIFIED UNSPECIFIED UNSPECIFIED Flak, Jonathan N. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-599656
DOI:	10.1210/endocr/bqab012
Journal or Publication Title:	Endocrinology
Volume:	162
Number:	4
Date:	2021
Publisher:	ENDOCRINE SOC
Place of Publication:	WASHINGTON
ISSN:	1945-7170
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYCLASE-ACTIVATING POLYPEPTIDE; BROWN ADIPOSE-TISSUE; VENTROMEDIAL HYPOTHALAMUS; FEEDING-BEHAVIOR; LEPTIN ACTION; NEURONS; RECEPTOR; GLUCOSE; HYPOGLYCEMIA; NUCLEUS Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59965