Endocannabinoid system activation may be associated with insulin resistance in women with polycystic ovary syndrome

Juan, Chi Chang; Chen, Kuo Hu; Wang, Peng Hui; Hwang, Jiann Loung; Seow, Kok-Min

doi:10.1016/j.fertnstert.2015.03.027

Cited by 26 publications

(17 citation statements)

References 30 publications

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“…Increased expression of CB1 in WAT is associated with hyperinsulinaemia, which is restored by CB1 antagonist administration (69) . In the present study, we observed increased CB1 and hyperinsulinaemia only in female HF offspring, which may contribute to insulin resistance (70,71) . CB1 expression in adipocytes is down-regulated by PPARγ (72) , and maternal HF diet decreased PPARγ content in the VIS WAT of female offspring.…”

Section: Discussionsupporting

confidence: 55%

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Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring

et al. 2017

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Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS's components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionsupporting

confidence: 55%

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring

et al. 2017

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“…The finding that metabolic risk factors are less severe in cannabis users compared to non-users could be explained by the interaction of cannabis with the endocannabinoid system via the cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptor. Over-activity of the endocannabinoid system is associated with an increased risk of developing abdominal obesity, hyperglycemia and dyslipidemia (Juan et al, 2015;Matias and Di Marzo, 2007). The main psychoactive constituent of cannabis (−)-trans-Δ 9 -tetrahydrocannabinol (THC) is a CB1 receptor agonist, which increases appetite and food intake and stimulates the storage of body fat (Di Marzo and Matias, 2005;Hillig and Mahlberg, 2004).…”

Section: Discussionmentioning

confidence: 99%

Cannabis use in people with severe mental illness: The association with physical and mental health – a cohort study. A Pharmacotherapy Monitoring and Outcome Survey study

et al. 2016

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“…In a nonpregnant canine model and in lean and obese human subjects, a HFD did not affect AEA but did decrease 2-AG concentrations (27,79). In contrast, 2-AG concentrations were increased in obesity and hyperphagia associated with Prader-Willi syndrome (45), in obese postmenopausal women with insulin resistance (1), and in women with polycystic ovarian syndrome (40). These controversial effects could be explained in part by the differences in insulin sensitivity in the different obesity-and HFD-related phenotypes; e.g., decreased insulin sensitivity is associated with increased 2-AG levels (1).…”

Section: Maternal Systemic and Hepatic Ecs Responses To Hfdmentioning

confidence: 90%

Effect of maternal high-fat diet on key components of the placental and hepatic endocannabinoid system

Gandhi

German

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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Maternal obesity in pregnancy has been linked to a spectrum of adverse developmental changes. Involvement of eCBs in obesity is well characterized. However, information regarding eCB physiology in obesity associated with pregnancy is sparse. This study evaluated fetomaternal hepatic, systemic, and placental eCB molecular changes in response to maternal consumption of a HFD. From ≥9 mo before conception, nonpregnant baboons ( Papio spp.) were fed a diet of either 45 (HFD; n = 11) or 12% fat or a control diet (CTR; n = 11), and dietary intervention continued through pregnancy. Maternal and fetal venous plasma samples were evaluated using liquid chromatography-mass spectrometry to quantify AEA and 2-AG. Placental, maternal and fetal hepatic tissues were analyzed using RT-PCR, Western blot, and immunohistochemistry. mRNA and protein expression of endocannabinoid receptors (CB1R and CB2R), FAAH, DAGL, MAGL, and COX-2 were determined. Statistical analyses were performed with the nonparametric Scheirer-Ray-Hare extension of the Kruskal-Wallis test to analyze the effects of diet (HFD vs. CTR), fetal sex (male vs. female), and the diet × sex interaction. Fetal weight was influenced by fetal sex but not by maternal diet. The increase in maternal weight in animals fed the HFD vs. the CTR diet approached significance ( P = 0.055). Maternal circulating 2-AG concentrations increased, and fetal circulating concentrations decreased in the HFD group, independently of fetal sex. CB1R receptor expression was detected in syncytiotrophoblasts (HFD) and the fetal endothelium (CTR and HFD). Placental CB2R protein expression was higher in males and lower in female fetuses in the HFD group. Fetal hepatic CB2R, FAAH, COX-2 (for both fetal sexes), and DAGLα (in male fetuses) protein expression decreased in the HFD group compared with the CTR group. We conclude that consumption of a HFD during pregnancy results in fetal systemic 2-AG and hepatic eCB deficiency.

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Endocannabinoid system activation may be associated with insulin resistance in women with polycystic ovary syndrome

Cited by 26 publications

References 30 publications

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring

Cannabis use in people with severe mental illness: The association with physical and mental health – a cohort study. A Pharmacotherapy Monitoring and Outcome Survey study

Effect of maternal high-fat diet on key components of the placental and hepatic endocannabinoid system

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