Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

Dalle, Sebastiaan; Koppo, Katrien

doi:10.1038/s41598-021-97859-3

Cited by 14 publications

(22 citation statements)

References 37 publications

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“…Another limiting factor may have been the different ages of the mice used in the short-term and long-term treatment experiments ( Willinghamm et al, 2010 ; Daroszewska et al, 2018 ). In the older animals, our results could be explained by low CB2 receptor expression, as the number of cannabinoid receptors on bone cells might also be altered at older ages, as has been shown for skeletal muscle ( Dalle and Koppo, 2021 ).…”

Section: Discussionsupporting

confidence: 54%

Impact of the Endocannabinoid System on Bone Formation and Remodeling in p62 KO Mice

et al. 2022

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Several studies have shown that the G-protein coupled cannabinoid receptor CB2 and its interaction partner p62 are molecularly involved in bone remodeling processes. Pharmacological activation of the CB2 receptor enhanced bone volume in postmenopausal osteoporosis and arthritis models in rodents, whereas knockout or mutation of the p62 protein in aged mice led to Paget’s disease of bone-like conditions. Studies of pharmacological CB2 agonist effects on bone metabolism in p62 KO mice have not been performed to date. Here, we assessed the effect of the CB2-specific agonist JWH133 after a short-term (5 days in 3-month-old mice) or long-term (4 weeks in 6-month-old mice) treatment on structural, dynamic, and cellular bone morphometry obtained by μCT of the femur and histomorphometry of the vertebral bodies in p62 KO mice and their WT littermates in vivo. A genotype-independent stimulatory effect of CB2 on bone formation, trabecular number, and trabecular thickness after short-term treatment and on tissue mineral density after long-term treatment was detected, indicating a weak osteoanabolic function of this CB2 agonist. Moreover, after short-term systemic CB2 receptor activation, we found significant differences at the cellular level in the number of osteoblasts and osteoclasts only in p62 KO mice, together with a weak increase in trabecular number and a decrease in trabecular separation. Long-term treatment showed an opposite JWH133 effect on osteoclasts in WT versus p62 KO animals and decreased cortical thickness only in treated p62 KO mice. Our results provide new insights into CB2 receptor signaling in vivo and suggest that CB2 agonist activity may be regulated by the presence of its macromolecular binding partner p62.

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Section: Discussionsupporting

confidence: 54%

Impact of the Endocannabinoid System on Bone Formation and Remodeling in p62 KO Mice

et al. 2022

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“…The above studies unfortunately lack data from other age groups. In human muscle, the CB1 protein levels seem to increase with age when compared between young (20–27 years) and old (≥65 years) individuals, and CB1 expression seems to increase with resistance exercise in older individuals [ 35 ]. Mice subjected to voluntary exercise for eight days exhibited increased eCB signaling in the Hip, accompanied by an increased progenitor cell proliferation within the DG.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis

Nidadavolu

Bilkei-Gorzó

Effah

et al. 2022

IJMS

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Endocannabinoid (eCB) signaling is markedly decreased in the hippocampus (Hip) of aged mice, and the genetic deletion of the cannabinoid receptor type 1 (CB1) leads to an early onset of cognitive decline and age-related histological changes in the brain. Thus, it is hypothesized that cognitive aging is modulated by eCB signaling through CB1. In the present study, we detailed the changes in the eCB system during the aging process using different complementary techniques in mouse brains of five different age groups, ranging from adolescence to old age. Our findings indicate that the eCB system is most strongly affected in middle-aged mice (between 9 and 12 months of age) in a brain region-specific manner. We show that 2-arachidonoylglycerol (2-AG) was prominently decreased in the Hip and moderately in caudate putamen (CPu), whereas anandamide (AEA) was decreased in both Cpu and medial prefrontal cortex along with cingulate cortex (mPFC+Cg), starting from 6 months until 12 months. Consistent with the changes in 2-AG, the 2-AG synthesizing enzyme diacylglycerol lipase α (DAGLα) was also prominently decreased across the sub-regions of the Hip. Interestingly, we found a transient increase in CB1 immunoreactivity across the sub-regions of the Hip at 9 months, a plausible compensation for reduced 2-AG, which ultimately decreased strongly at 12 months. Furthermore, quantitative autoradiography of CB1 revealed that [3H]CP55940 binding markedly increased in the Hip at 9 months. However, unlike the protein levels, CB1 binding density did not drop strongly at 12 months and at old age. Furthermore, [3H]CP55940 binding was significantly increased in the lateral entorhinal cortex (LEnt), starting from the middle age until the old age. Altogether, our findings clearly indicate a middle-age crisis in the eCB system, which could be a potential time window for therapeutic interventions to abrogate the course of cognitive aging.

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“…It is possible that muscle type is an important determinant of CB 1 expression. Indeed, immunohistochemistry data from our lab showed that CB 1 expression was higher in slow human (MyHC + ) compared to fast human (MyHCI – ) muscle fibers (Dalle & Koppo, 2021). Unpublished data from our lab confirmed these findings in murine whole‐muscle tissue, as CB 1 protein expression was significantly higher in the slow m. Soleus compared to the faster m. Gastrocnemius and m. Quadriceps (Figure 5).…”

Section: Cannabinoid System and Muscle Homeostasis: Paths And Challengesmentioning

confidence: 99%

“…Indeed, CB 1 gene expression was higher in the m. Gastrocnemius of 16‐month‐old compared to 4‐month‐old mice (Lipina et al, 2016). Accordingly, recent work indicated that CB 1 protein expression was significantly higher (~25%) in the m. Vastus Lateralis of old (65–84 years) compared to young adults (20–27 years) (Dalle & Koppo, 2021). However, Le Bacquer et al found CB 1 gene and protein expression to be lower in the m. Soleus , but not in the m. Extensor Digitorum Longus, of old (24 months) versus adult (6 months) rats (Le Bacquer, Salles, et al, 2021).…”

Section: Cannabinoid System and Muscle Homeostasis: Paths And Challengesmentioning

confidence: 99%

Molecular networks underlying cannabinoid signaling in skeletal muscle plasticity

Dalle

Schouten

Meeus

et al. 2022

Journal Cellular Physiology

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The cannabinoid system is ubiquitously present and is classically considered to engage in neural and immunity processes. Yet, the role of the cannabinoid system in the whole body and tissue metabolism via central and peripheral mechanisms is increasingly recognized. The present review provides insights in (i) how cannabinoid signaling is regulated via receptor-independent and -dependent mechanisms and (ii) how these signaling cascades (might) affect skeletal muscle plasticity and physiology.Receptor-independent mechanisms include endocannabinoid metabolism to eicosanoids and the regulation of ion channels. Alternatively, endocannabinoids can act as ligands for different classic (cannabinoid receptor 1 [CB 1 ], CB 2 ) and/or alternative (e.g., TRPV1, GPR55) cannabinoid receptors with a unique affinity, specificity, and intracellular signaling cascade (often tissue-specific). Antagonism of CB 1 might hold clues to improve oxidative (mitochondrial) metabolism, insulin sensitivity, satellite cell growth, and muscle anabolism, whereas CB 2 agonism might be a promising way to stimulate muscle metabolism and muscle cell growth. Besides, CB 2 ameliorates muscle regeneration via macrophage polarization toward an anti-inflammatory phenotype, induction of MyoD and myogenin expression and antifibrotic mechanisms. Also TRPV1 and GPR55 contribute to the regulation of muscle growth and metabolism. Future studies should reveal how the cannabinoid system can be targeted to improve muscle quantity and/or quality in conditions such as ageing, disease, disuse, and metabolic dysregulation, taking into account challenges that are inherent to modulation of the cannabinoid system, such as central and peripheral side effects.

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Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

Cited by 14 publications

References 37 publications

Impact of the Endocannabinoid System on Bone Formation and Remodeling in p62 KO Mice

Impact of the Endocannabinoid System on Bone Formation and Remodeling in p62 KO Mice

Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis

Molecular networks underlying cannabinoid signaling in skeletal muscle plasticity

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