caryophyllene and Obesity

Food addiction (FA) is a psychological construct that may be involved in the etiology of obesity. The cannabinoid system is involved in the addictive-like food preferences by acting on the dopaminergic pathway of the brain. β-caryophyllene is a dietary cannabinoid that is a cannabinoid type 2 (CB2) receptor agonist. This study explored the impacts of β-caryophyllene supplementation on eating behavior, appetite, mental health, anthropometric parameters, body composition, and some hormones related to appetite in women with obesity diagnosed with FA. Women with obesity and FA, diagnosed by the Yale Food Addiction Scale Score (YFAS-S) ≥3, were randomly allocated to receive a β-caryophyllene softgel (n = 26) (100 mg/daily with meal) or placebo (n = 26) for 8 weeks. Anthropometric measurements, body composition, eating behavior, biochemical markers, dietary intake, appetite, stress, anxiety, and depression were evaluated during the study period. β-caryophyllene administration significantly reduced YFAS-S compared to the placebo group (changes in FA score: 1.5 ± 0.9 vs. - 0.7 ± 1.4; corrected P = 0.05). Serum levels of orexin-A significantly decreased in the β-caryophyllene group (p = 0.02); however, no significant difference was observed compared to the placebo group (corrected P = 0.09). β-caryophyllene supplementation had no significant effect on body composition, anthropometric indices, appetite, eating behavior, dietary intake, physical activity level, mental health, and levels of oxytocin and neuropeptide Y (NPY), compared to the placebo. β-caryophyllene supplementation may have beneficial effects on improving YFAS-S in women with obesity diagnosed with FA. TRIAL REGISTRATION: Iranian Registry of Clinical Trials identifier: IRCT20200914048712N1.

Topics: Cannabinoids; Feeding Behavior; Female; Food Addiction; Humans; Iran; Obesity; Polycyclic Sesquiterpenes; Surveys and Questionnaires

Obesity is an abnormal or excessive accumulation of fat in the body that exacerbates metabolic and inflammatory processes, and impairs the health of afflicted individuals. β-caryophyllene is a natural sesquiterpene that is a dietary cannabinoid with anti-inflammatory properties and potential activity against metabolic diseases. In the present study, we evaluated the effect of β-caryophyllene on C57BL/6 mice using a diet-induced obesity model. Male mice were randomly assigned to the following groups over a 16-week period: (1) standard diet as lean control, (2) high-fat diet (HFD) as obese control, and (3) HFD + β-caryophyllene with β-caryophyllene at 50 mg/kg. Treatment with β-caryophyllene improved various metabolic parameters including increased total body weight, fasting glucose levels, oral-glucose tolerance, insulin tolerance, fasting triglycerides, adipocyte hypertrophy, and liver macrovesicular steatosis. β-caryophyllene also modulated the levels and expression of immune response factors including adiponectin, leptin, insulin, interleukin-6, tumor necrosis factor-a, and Toll-like receptor-4. Our data indicate that chronic supplementation with β-caryophyllene can improve relevant metabolic and immunological processes in obese mice. This protocol was approved by the Institutional Committee for Care and Use of Laboratory Animals from the University of Guadalajara with protocol code CUCEI/CINV/CICUAL-01/2022.

Topics: Adiponectin; Animals; Anti-Inflammatory Agents; Blood Glucose; Cannabinoids; Diet, High-Fat; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Polycyclic Sesquiterpenes; Triglycerides; Tumor Necrosis Factors; Weight Gain

Obesity is an excessive accumulation of fat that exacerbates the metabolic and inflammatory processes. Studies associate these processes with conditions and dysregulation in the intestinal tract, increased concentrations of lipopolysaccharides (LPSs) in the blood, differences in the abundance of intestinal microbiota, and the production of secondary metabolites such as short-chain fatty acids. β-Caryophyllene (BCP) is a natural sesquiterpene with anti-inflammatory properties and with the potential purpose of fighting metabolic diseases. A diet-induced obesity model was performed in 16-week-old C57BL/6 mice administered with BCP [50 mg/kg]. A reduction in the expression of Claudin-1 was observed in the group with a high-fat diet (HFD), which was caused by the administration of BCP; besides BCP, the

Topics: Animals; Claudin-1; Diet, High-Fat; Fatty Acids; Gastrointestinal Diseases; Leptin; Mice; Mice, Inbred C57BL; Obesity; Polycyclic Sesquiterpenes; Sesquiterpenes; Sexually Transmitted Diseases

Obesity worsens airway hyperresponsiveness (AHR) in asthmatic subjects by up-regulating macrophage polarization that leads to excessive secretion of pro-inflammatory adipokines from white adipose tissue followed by generation of oxidative stress in the respiratory system. Treatment through conventional signaling pathways proved to be inadequate in obese asthmatics, so a therapeutical approach through a non-conventional pathway may prove to be effective.. This study aimed to investigate the efficacy of a FDA-approved food additive, β-caryophyllene (BCP) in obesity-associated AHR.. A repertoire of protein expression, cytokine and adiponectin estimation, oxidative stress assays, histopathology, and fluorescence immune-histochemistry were performed to assess the efficacy of BCP in C57BL/6 mice model of obesity-associated AHR. Additionally, human adipocyte was utilized to study the effect of BCP on macrophage polarization in Boyden chamber cell culture inserts.. Obesity-associated AHR is ameliorated by administration of BCP by inhibition of the macrophage polarization by activation of AMPKα, Nrf2/HO-1 and AdipoR1 and AdipoR2 signaling pathway, up-regulation of adiponectin, GLP-1, IFN-γ, SOD, catalase and down-regulation of NF-κB, leptin, IL-4, TNF, and IL-1β. Browning of eWAT by induction of thermogenesis and activation of melanocortin pathway also contributed to the amelioration of obesity-associated AHR. We conclude that BCP ameliorated the obesity-associated AHR via inhibition of macrophage polarization, activation of AMPKα, Nrf2/HO-1, and up-regulation of AdipoR1 and AdipoR2 expression and down-regulation of NFκB expression in lung of animal.. Being an FDA-approved food additive, BCP may prove to be a safe and potential agent against obesity-associated AHR.

Topics: Adipocytes; Animals; Cells, Cultured; Humans; Mice; Mice, Inbred C57BL; Obesity; Polycyclic Sesquiterpenes; Respiratory Hypersensitivity

Insulin resistance (IR) and obesity predispose diseases such as diabetes, cardiovascular and neurodegenerative disorders. Beta-caryophyllene (BCP), a natural sesquiterpene, exerts neuroprotective, anxiolytic and antidepressant effects via its selective agonism to cannabinoid receptor 2 (CB2R). BCP was shown to have an anti-diabetic effect, however, the implication of CB2R is yet to be elucidated. A link between CB2R agonism and PPAR-γ activation has been discussed, but the exact mechanism is not well-defined. This study was designed to examine the role of BCP in improving diet-induced metabolic (insulin resistance), neurobehavioral (anxiety, depression and memory deficit), and neurochemical (oxidative, inflammatory and neurotrophic factor) alterations in the prefrontal cortex of obese rats' brain. The involvement of CB2R and/or PPAR-γ dependent activity was also investigated.. Male Wistar rats were fed a high fat/fructose diet (HFFD) for 12 weeks to induce IR and obesity. Rats were treated with BCP for the last 4 weeks. Either CB2R antagonist AM630 or PPAR-γ antagonist BADGE was administered before BCP treatment to study the mechanism of BCP actions.. Beta-caryophyllene alleviated HFFD-induced IR, oxidative-stress, neuroinflammation and behavioral changes. The anxiolytic, anti-oxidant and anti-inflammatory effects of BCP were mediated by both PPAR-γ and CB2R. The effects of BCP on glycemic parameters seem to be CB2R-dependent with the non-significant role of PPAR-γ. Furthermore, BCP-evoked antidepressant and memory improvement are likely mediated only via CB2R, mainly by upregulation of PGC-1α and BDNF.. This study suggests the potential effect of BCP in treating HFFD-induced metabolic and neurobehavioral alterations. BCP seems to activate PPAR-γ in a ligand-independent manner, via upregulation and activation of PGC-1α. The BCP activation of PPAR--γ seems to be CB2R-dependent.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Diet, High-Fat; Fructose; Male; Maze Learning; Memory Disorders; Obesity; Oxidative Stress; Polycyclic Sesquiterpenes; PPAR gamma; Rats; Rats, Wistar; Receptor, Cannabinoid, CB2; Sesquiterpenes

We reported previously that high-fat diet (HFD) feeding stimulated solid tumor growth and lymph node (LN) metastasis in C57BL/6N mice injected with B16F10 melanoma cells. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils and has been shown to exert anti-inflammatory activities. To examine whether BCP inhibits HFD-induced melanoma progression, 4-weeks old, male C57BL/6N mice were fed a control diet (CD, 10 kcal% fat) or HFD (60 kcal% fat + 0, 0.15 or 0.3% BCP) for the entire experimental period. After 16 weeks of feeding, B16F10s were subcutaneously injected into mice. Three weeks later, tumors were resected, and mice were killed 2 weeks post-resection. Although HFD feeding increased body weight gain, fasting blood glucose levels, solid tumor growth, LN metastasis, tumor cell proliferation, angiogenesis and lymphangiogenesis, it decreased apoptotic cells, all of which were suppressed by dietary BCP. HFD feeding increased the number of lipid vacuoles and F4/80+ macrophage (MΦ) and macrophage mannose receptor (MMR)+ M2-MΦs in tumor tissues and adipose tissues surrounding the LN, which was suppressed by BCP. HFD feeding increased the levels of CCL19 and CCL21 in the LN and the expression of CCR7 in the tumor; these changes were blocked by dietary BCP. In vitro culture results revealed that BCP inhibited lipid accumulation in 3T3-L1 preadipocytes; monocyte migration and monocyte chemoattractant protein-1 secretion by B16F10s, adipocytes and M2-MΦs; angiogenesis and lymphangiogenesis. The suppression of adipocyte and M2-cell accumulation and the inhibition of CCL19/21-CCR7 axis may be a part of mechanisms for the BCP suppression of HFD-stimulated melanoma progression.

Topics: 3T3 Cells; Adipocytes; Animals; Antineoplastic Agents; Body Weight; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemokine CCL19; Chemokine CCL2; Chemokine CCL21; Diet, High-Fat; Dietary Fats; Lectins, C-Type; Lymph Nodes; Lymphatic Metastasis; Macrophages; Male; Mannose Receptor; Mannose-Binding Lectins; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Obese; Neovascularization, Pathologic; Obesity; Polycyclic Sesquiterpenes; Random Allocation; Receptors, CCR7; Receptors, Cell Surface; Sesquiterpenes; Skin Neoplasms; Subcutaneous Fat; Vacuoles; Weight Gain