Dataset Information

Expression of Functional Cannabinoid Type-1 (CB₁) Receptor in Mitochondria of White Adipocytes.

ABSTRACT: Via activation of the cannabinoid type-1 (CB₁) receptor, endogenous and exogenous cannabinoids modulate important biochemical and cellular processes in adipocytes. Several pieces of evidence suggest that alterations of mitochondrial physiology might be a possible mechanism underlying cannabinoids' effects on adipocyte biology. Many reports suggest the presence of CB₁ receptor mRNA in both white and brown adipose tissue, but the detailed subcellular localization of CB₁ protein in adipose cells has so far been scarcely addressed. In this study, we show the presence of the functional CB₁ receptor at different subcellular locations of adipocytes from epididymal white adipose tissue (eWAT) depots. We observed that CB₁ is located at different subcellular levels, including the plasma membrane and in close association with mitochondria (mtCB₁). Functional analysis in tissue homogenates and isolated mitochondria allowed us to reveal that cannabinoids negatively regulate complex-I-dependent oxygen consumption in eWAT. This effect requires mtCB₁ activation and consequent regulation of the intramitochondrial cAMP-PKA pathway. Thus, CB₁ receptors are functionally present at the mitochondrial level in eWAT adipocytes, adding another possible mechanism for peripheral regulation of energy metabolism.

SUBMITTER: Pagano Zottola AC

PROVIDER: S-EPMC9406404 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Expression of Functional Cannabinoid Type-1 (CB1) Receptor in Mitochondria of White Adipocytes.

Pagano Zottola Antonio C AC Severi Ilenia I Cannich Astrid A Ciofi Philippe P Cota Daniela D Marsicano Giovanni G Giordano Antonio A Bellocchio Luigi L

Cells 20220819 16

Via activation of the cannabinoid type-1 (CB1) receptor, endogenous and exogenous cannabinoids modulate important biochemical and cellular processes in adipocytes. Several pieces of evidence suggest that alterations of mitochondrial physiology might be a possible mechanism underlying cannabinoids' effects on adipocyte biology. Many reports suggest the presence of CB1 receptor mRNA in both white and brown adipose tissue, but the detailed subcellular localization of CB1< ...[more]

PMID: 36010658

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Project description:Background: The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation, and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues. However, no study has investigated differential expression of the endocannabinoid system in labor. Objectives: The purpose of this study was to identify and quantify two components of the endocannabinoid system, the CB1 cannabinoid receptor and cannabinoid receptor interacting protein 1a (CRIP1a) in uterine and placental tissues, and to determine if there is differential expression in tissues exposed to labor. We hypothesized that CB1 cannabinoid receptor concentration would be altered in uterine and placental tissue exposed to labor compared with tissues not exposed to labor. Study Design: Uterine and placental tissue samples were collected in nine laboring and 11 nonlaboring women undergoing cesarean delivery. CB1 cannabinoid receptor and CRIP1a presence and quantification were evaluated using western blot, immunohistochemistry, and real-time quantitative polymerase chain reaction. Statistical comparisons of laboring and nonlaboring subjects were made for uterine and placental tissue using a Mann-Whitney test. Results: Immunohistochemistry demonstrated positive staining for CB1 cannabinoid receptors and CRIP1a in uterine tissue. The protein abundance of CB1 cannabinoid receptor in uterine tissue was significantly lower in tissues exposed to labor (p=0.01). The protein abundance of CRIP1a was lower in uterine tissue exposed to labor but did not reach statistical significance (p=0.06). mRNA expression of CB1 cannabinoid receptor (p=0.20) and CRIP1a (p=0.63) did not differ in labored compared with nonlabored uterine tissues. Conclusions: Our findings of diminished protein density of CB1 cannabinoid receptor in uterine tissue exposed to labor support the hypothesis that the endocannabinoid system plays a role in parturition. Our data add to the growing body of evidence indicating the endocannabinoid system is of importance for successful reproduction and support the need for additional research investigating this complex system as it pertains to labor. ClinicalTrials.gov ID: NCT03752021.

Dataset Information

Expression of Functional Cannabinoid Type-1 (CB₁) Receptor in Mitochondria of White Adipocytes.

Publications

Expression of Functional Cannabinoid Type-1 (CB<sub>1</sub>) Receptor in Mitochondria of White Adipocytes.

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