Category Archives: Obesity

Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues.

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“The endocannabinoid (eCB) system is widely expressed in many central and peripheral tissues, and is involved in a plethora of physiological processes. Among these, activity of the eCB system promotes energy intake and storage, which, however, under pathophysiological conditions, can favour the development of obesity and obesity-related disorders. It is proposed that eCB signalling is evolutionary beneficial for survival under periods of scarce food resources. Remarkably, eCB signalling is increased both in hunger and in overnutrition conditions, such as obesity and type-2 diabetes. This apparent paradox suggests a role of the eCB system both at initiation and at clinical endpoint of obesity. This review will focus on recent findings about the role of the eCB system controlling whole-body metabolism in mice that are genetically modified selectively in different cell types. The current data in fact support the notion that eCB signalling is not only engaged in the development but also in the maintenance of obesity, whereby specific cell types in central and peripheral tissues are key sites in regulating the entire body’s energy homeostasis.”

https://www.ncbi.nlm.nih.gov/pubmed/30599065

https://link.springer.com/article/10.1007%2Fs00018-018-2994-6

Theoretical Explanation for Reduced Body Mass Index and Obesity Rates in Cannabis Users

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“Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s.

Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB1R and leading to increased caloric intake, reduced metabolic rates, and weight gain.

Cannabis, or THC, also stimulates CB1R and increases caloric intake during acute exposures.

The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake.

We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB1R following acute Cannabis consumption reduces energy storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

Evidence suggests that, in the United States, many people may actually achieve net health benefits from moderate Cannabis use, due to reduced risk of obesity and associated diseases.”

https://www.liebertpub.com/doi/10.1089/can.2018.0045?_ga=2.221453528.1791159238.1546024140-1083808004.1546024140

“Reduced Body Mass Index and Obesity Rates in Cannabis Users”  https://www.genengnews.com/insights/reduced-body-mass-index-and-obesity-rates-in-cannabis-users/?fbclid=IwAR3a0wbfGoPwAR-pYQGCeLz-KYUFdiLJoj6Ja7rTTNGBYwkjIGw1fUjf5LI

 

Associations between cannabis use and cardiometabolic risk factors: A longitudinal study of men.

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“This study tested longitudinal associations between cannabis use and cardiometabolic risk factors that underlie the development of cardiovascular diseases.

RESULTS:

Greater cannabis exposure was associated with relatively lower BMI (β=-0.31, p<.001), smaller WHR (β=-0.23, p=.002), better HDL (β=0.14, p=.036) and LDL cholesterol (β=-0.15, p=.026), lower triglycerides (β=-0.17, p=.009), lower fasting glucose (β=-0.15, p<.001) and HOMA-IR (β=-0.21, p=.003), lower systolic (β=-0.22, p<.001) and diastolic blood pressure (β=-0.15, p=.028), and fewer metabolic syndrome criteria (β=-0.27, p<.001). With exception of BMI, cannabis users’ mean levels on cardiometabolic risk factors were generally below clinical cutoffs for high risk. Most associations between cannabis use and cardiometabolic risk factors remained after adjusting for tobacco use, childhood SES, and childhood health. However, after adjusting for adult BMI, these associations were no longer apparent, and mediation tests suggested that cannabis users’ relatively lower BMI might explain their lower levels of risk on other cardiometabolic risk factors.

CONCLUSIONS:

Cannabis use is associated with lower BMI, and lower BMI is related to lower levels of risk on other cardiometabolic risk factors.”

https://www.ncbi.nlm.nih.gov/pubmed/30589665

https://insights.ovid.com/crossref?an=00006842-900000000-98666

Bidirectional modulation of food habit expression by the endocannabinoid system.

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“The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal-directed actions.

The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear.

Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice.

We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding.

Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co-administration of an enzyme inhibitor that selectively increases the endocannabinoid 2-arachidonoyl glycerol (2-AG) with AM404 partially restored habitual responding for food.

Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/30589475

https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14330

Weight loss and improved mood after aerobic exercise training are linked to lower plasma anandamide in healthy people.

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Physiology & Behavior

“Anandamide, a major endocannabinoid, participates in energy metabolism homeostasis and neurobehavioral processes. In a secondary analyses of an open-label, randomized controlled trial, we investigated the long-term effect of aerobic exercise on resting plasma anandamide, and explored its relationship with changes in body weight, cardiorespiratory fitness, and mood status in healthy, physically inactive individuals.

Thirty-four participants (age = 38 ± 11.5, BMI = 26.6 ± 3.6) were intention to treat-analysed (Exercise: n = 17; Control: n = 17). After intervention, there were significant decreases in plasma anandamide (p < .01), anger, anxiety, and body weight (all p < .05), whereas cardiorespiratory fitness increased (p < .05) in the exercise group. There were no significant changes in any variable for the control group. In the whole cohort, adjusted R2 of multiple linear regressions showed that 12.2% of change body weight was explained by changes in anandamide (β = 0.391, p = .033), while 27% of change in mood disturbance (β = 0.546, p = .003), and 13.1% of change in anger (β = 0.404, p = .03) was explained by changes in anandamide.

Our data suggest that the weight loss and mood improvement through regular moderate exercise may involve changes in anandamide metabolism/signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/30578894

https://www.sciencedirect.com/science/article/abs/pii/S0031938418308254?via%3Dihub

Cannabinoid-1 Receptor Antagonism Improves Glycemic Control and Increases Energy Expenditure via Sirt1/mTORC2 and AMPK Signaling.

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“Endocannabinoids promote energy conservation in obesity, whereas cannabinoid-1 receptor (CB1 R) blockade reverses body weight gain and insulin resistance and increases energy expenditure.

Here we investigated the molecular mechanisms of the catabolic effects of CB1 R blockade in the liver.

CONCLUSION: peripheral CB1 R blockade in obese mice improves glycemic control via the hepatic Sirt1/mTORC2/Akt pathway, whereas it increases fatty acid oxidation via LKB1/AMPK signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/30506571

https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.30364

Cannabinoid receptor type-1 partially mediates metabolic endotoxemia-induced inflammation and insulin resistance.

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Physiology & Behavior

“Cannabinoid receptor type-1 partially mediates metabolic endotoxemia-induced inflammation and insulin resistance. Despite no significant differences in body weight among groups, chronic exposure to low-level LPS altered hepatic endocannabinoid signaling, increased inflammation, and impaired insulin sensitivity and insulin clearance. CB1 inhibition significantly attenuated LPS signaling, which attenuated LPS-induced metabolic alterations. Therefore, we concluded that CB1 contributes to LPS-mediated inflammation and insulin resistance, suggesting that blocking CB1 signaling may have therapeutic benefits in reducing inflammation-induced metabolic abnormalities.”

https://www.ncbi.nlm.nih.gov/pubmed/30502357

https://www.sciencedirect.com/science/article/abs/pii/S0031938418304190?via%3Dihub

Cannabinoids, Chemical Senses, and Regulation of Feeding Behavior.

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“The herb Cannabis sativa has been traditionally used in many cultures and all over the world for thousands of years as medicine and recreation.

However, because it was brought to the Western world in the late 19th century, its use has been a source of controversy with respect to its physiological effects as well as the generation of specific behaviors. In this regard, the CB1 receptor represents the most relevant target molecule of cannabinoid components on nervous system and whole-body energy homeostasis.

Thus, the promotion of CB1 signaling can increase appetite and stimulate feeding, whereas blockade of CB1 suppresses hunger and induces hypophagia.

Taste and flavor are sensory experiences involving the oral perception of food-derived chemicals and drive a primal sense of acceptable or unacceptable for what is sampled. Therefore, research within the last decades focused on deciphering the effect of cannabinoids on the chemical senses involved in food perception and consequently in the pattern of feeding.

In this review, we summarize the data on the effect of cannabinoids on chemical senses and their influences on food intake control and feeding behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30481264

Inhibition of Cannabinoid Receptor 1 Can Influence the Lipid Metabolism in Mice with Diet-Induced Obesity.

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“A growing number of evidences accumulated about critical metabolic role of cannabinoid type 1 receptor (CB1), carnitine palmitoyltransferase-1 (CPT1) and peroxisome proliferator-activated receptors (PPARs) in some peripheral tissues, including adipose tissue, liver, skeletal muscle and heart.

Taken together, these data indicate that the inhibition of CB1 could ameliorate lipid metabolism via the stimulation of the CPT1A and CPT1B expression in vivo. Simultaneously, the PPARα and PPARγ expression levels significantly differed compared to that of PPARβ in obesity and lipid metabolism-related disorders under blockade of CB1.

Both the mechanism of the influence of CB1 inhibition on lipid metabolism in the examined tissues and the specific mechanism of PPARα, PPARγ and PPARβ involvement in lipid exchange under these conditions remain to be further elucidated.”

https://www.ncbi.nlm.nih.gov/pubmed/30472964

https://link.springer.com/article/10.1134%2FS0006297918100127

The protective effects of Δ9 -tetrahydrocannabinol against inflammation and oxidative stress in rat liver with fructose-induced hyperinsulinemia.

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“A large amount of fructose is metabolized in the liver and causes hepatic functional damage. Δ9 -tetrahydrocannabinol (THC) is known as a therapeutic agent for clinical and experimental applications.

 

The study aims to investigate the effects of THC treatment on inflammation, lipid profiles and oxidative stress in rat liver with hyperinsulinemia.

 

According to the result, long-term and low-dose THC administration may reduce hyperinsulinemia and inflammation in rats to some extent.”

 

https://www.ncbi.nlm.nih.gov/pubmed/30427077

https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.13042