Cannabinoid Receptor 1 Blockade Attenuates Obesity and Adipose Tissue Type 1 Inflammation Through miR-30e-5p Regulation of Delta-Like-4 in Macrophages and Consequently Downregulation of Th1 Cells

Miranda, Kathryn; Mehrpouya-Bahrami, Pegah; Nagarkatti, Prakash

doi:10.3389/fimmu.2019.01049

Cited by 39 publications

(39 citation statements)

References 42 publications

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“…HFD increased body weight, fasting glucose, and IR, but also promoted adipose tissue inflammation characterized by inflammatory M1 macrophage infiltration. 61 Another study confirmed the HFD-induced M1-M2 imbalance in WAT and the abnormalities in glycemic indexes and lipid profiles. 62 Guo et al 63 fed 2-month-old male C57BL/6 mice with either HFD (45% energy from fat) including 7% sucrose or low-fat diet (LFD; 10% energy from fat).…”

Section: Dietary Interventionsmentioning

confidence: 83%

Cardiometabolic Syndrome: An Update on Available Mouse Models

et al. 2020

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Cardiometabolic syndrome (CMS), a disease entity characterized by abdominal obesity, insulin resistance (IR), hypertension, and hyperlipidemia, is a global epidemic with approximately 25% prevalence in adults globally. CMS is associated with increased risk for cardiovascular disease (CVD) and development of diabetes. Due to its multifactorial etiology, the development of several animal models to simulate CMS has contributed significantly to the elucidation of the disease pathophysiology and the design of therapies. In this review we aimed to present the most common mouse models used in the research of CMS. We found that CMS can be induced either by genetic manipulation, leading to dyslipidemia, lipodystrophy, obesity and IR, or obesity and hypertension, or by administration of specific diets and drugs. In the last decade, the ob/ob and db/db mice were the most common obesity and IR models, whereas Ldlr−/− and Apoe−/− were widely used to induce hyperlipidemia. These mice have been used either as a single transgenic or combined with a different background with or without diet treatment. High-fat diet with modifications is the preferred protocol, generally leading to increased body weight, hyperlipidemia, and IR. A plethora of genetically engineered mouse models, diets, drugs, or synthetic compounds that are available have advanced the understanding of CMS. However, each researcher should carefully select the most appropriate model and validate its consistency. It is important to consider the differences between strains of the same animal species, different animals, and most importantly differences to human when translating results.

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Section: Dietary Interventionsmentioning

confidence: 83%

Cardiometabolic Syndrome: An Update on Available Mouse Models

et al. 2020

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“…Other innate immune cells are also regulated by endocannabinoids. Both murine and human monocytes/macrophages and microglial cells, express the CB1 and CB2 receptors [ 16 , 37 , 38 , 39 , 40 , 41 ]. Research by Acharya et al showed that the engagement of the cannabinoid receptors augments the number and immune suppressive function of the regulatory CX3CR1hi macrophages in the gut [ 42 ].…”

Section: The Roles Of the Endocannabinoid System In Immunitymentioning

confidence: 99%

Cannabis, the Endocannabinoid System and Immunity—the Journey from the Bedside to the Bench and Back

Almogi-Hazan

2020

IJMS

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The Cannabis plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system. Cannabinoids affect the nervous system and play significant roles in the regulation of the immune system. While Cannabis is not yet registered as a drug, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries to authorize their clinical use. However, the data from basic and medical research dedicated to medical Cannabis is currently limited. A variety of pathological conditions involve dysregulation of the immune system. For example, in cancer, immune surveillance and cancer immuno-editing result in immune tolerance. On the other hand, in autoimmune diseases increased immune activity causes tissue damage. Immuno-modulating therapies can regulate the immune system and therefore the immune-regulatory properties of cannabinoids, suggest their use in the therapy of immune related disorders. In this contemporary review, we discuss the roles of the endocannabinoid system in immunity and explore the emerging data about the effects of cannabinoids on the immune response in different pathologies. In addition, we discuss the complexities of using cannabinoid-based treatments in each of these conditions.

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“…AM 251 treatment also significantly reduced the tubular cross-sectional diameter of the kidney, compared to vehicle ( p < 0.05), indicating that AM 251 protects from obesity-related kidney damage [ 61 ]. Furthermore, AM 251 treatment in the DIO mice was found to substantially decrease the levels of adipose tissue inflammation, in addition to the expected weight loss [ 62 ]. Clearly, AM 251 is a promising CB1 inverse agonist, but at this time, no clinical research has been conducted.…”

Section: Exploring the Direct Effects Of Cannabinoid Drugs On Bodymentioning

confidence: 99%

Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs

Murphy

Foll

2020

Biomolecules

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Obesity rates are increasing worldwide and there is a need for novel therapeutic treatment options. The endocannabinoid system has been linked to homeostatic processes, including metabolism, food intake, and the regulation of body weight. Rimonabant, an inverse agonist for the cannabinoid CB1 receptor, was effective at producing weight loss in obese subjects. However, due to adverse psychiatric side effects, rimonabant was removed from the market. More recently, we reported an inverse relationship between cannabis use and BMI, which has now been duplicated by several groups. As those results may appear contradictory, we review here preclinical and clinical studies that have studied the impact on body weight of various cannabinoid CB1 drugs. Notably, we will review the impact of CB1 inverse agonists, agonists, partial agonists, and neutral antagonists. Those findings clearly point out the cannabinoid CB1 as a potential effective target for the treatment of obesity. Recent preclinical studies suggest that ligands targeting the CB1 may retain the therapeutic potential of rimonabant without the negative side effect profile. Such approaches should be tested in clinical trials for validation.

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Cannabinoid Receptor 1 Blockade Attenuates Obesity and Adipose Tissue Type 1 Inflammation Through miR-30e-5p Regulation of Delta-Like-4 in Macrophages and Consequently Downregulation of Th1 Cells

Cited by 39 publications

References 42 publications

Cardiometabolic Syndrome: An Update on Available Mouse Models

Cardiometabolic Syndrome: An Update on Available Mouse Models

Cannabis, the Endocannabinoid System and Immunity—the Journey from the Bedside to the Bench and Back

Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs

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