Sex hormones influence expression and function of peroxisome proliferator-activated receptor γ in adipocytes: pathophysiological aspects

Sato, Hiromi; Ishikawa, Masatoshi; Sugai, Hana; Funaki, Asami; Kimura, Yuki; Sumitomo, Mai; Ueno, Koichi

doi:10.1515/hmbci-2014-0026

Cited by 11 publications

(6 citation statements)

References 49 publications

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“…Multiple direct or indirect modes of action could be conjectured to be responsible for the gender-specific effects of DOSS on offspring in the model presented. For example, direct effects could occur via PPAR signaling and sexually dimorphic expression of PPARγ and protein partners or co-factors 70,71 . Downstream or indirect effects could be mediated via the placenta.…”

Section: Discussionmentioning

confidence: 99%

Increased adiposity, inflammation, metabolic disruption and dyslipidemia in adult male offspring of DOSS treated C57BL/6 dams

Temkin

Bowers

Ulmer

et al. 2019

Sci Rep

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Evidence indicates that obesity can be promoted by chemical ‘obesogens’ that drive adiposity, hunger, inflammation and suppress metabolism. Dioctyl sodium sulfosuccinate (DOSS), a lipid emulsifier and candidate obesogen in vitro, is widely used in processed foods, cosmetics and as stool softener medicines commonly used during pregnancy. In vivo testing of DOSS was performed in a developmental origins of adult obesity model. Pregnant mice were orally administered vehicle control or DOSS at times and doses comparable to stool softener use during human pregnancy. All weaned offspring consumed only standard diet. Adult male but not female offspring of DOSS-treated dams showed significantly increased body mass, overall and visceral fat masses, and decreased bone area. They exhibited significant decreases in plasma adiponectin and increases in leptin, glucose intolerance and hyperinsulinemia. Inflammatory IL-6 was elevated, as was adipose Cox2 and Nox4 gene expressions, which may be associated with promoter DNA methylation changes. Multiple significant phospholipid/sterol lipid increases paralleled profiles from long-term high-fat diet induced obesity in males. Collectively, developmental DOSS exposure leads to increased adult adiposity, inflammation, metabolic disorder and dyslipidemia in offspring fed a standard diet, suggesting that pharmaceutical and other sources of DOSS taken during human pregnancy might contribute to long-term obesity-related health concerns in offspring.

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Section: Discussionmentioning

confidence: 99%

Increased adiposity, inflammation, metabolic disruption and dyslipidemia in adult male offspring of DOSS treated C57BL/6 dams

Temkin

Bowers

Ulmer

et al. 2019

Sci Rep

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“…Because of this important role on insulin sensitivity, adiponectin is currently one of the strongest biochemical predictors of type 2 diabetes mellitus [ 47 ]. However, sex hormons can modify the expression and activities of PPARγ and its downstream adipokines [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population

et al. 2016

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BackgroundThere is little data on the metabolic effects of adipokines in sub-Saharan African populations. This study aimed to explore the potential relationship of leptin and adiponectin, with obesity, plasma lipids and insulin resistance in a Cameroonian population.MethodsWe enrolled 167 men and 309 women aged ≥18 years from the general population in Cameroon. Data were collected on waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), body fat (BF%), fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). Pearson’s correlation and multiple stepwise linear regression analyses were used to determine correlates of leptin and adiponectin serum levels.ResultsThe prevalence of obesity was higher in women compared to men (p < 0.0001), and Central obesity which is more prevalent particularly in women (WC = 42.4 %, WHR = 42.3 %), is almost for 90 % comparable to %BF (42.7 %).Adiponectin negatively with BMI (r = −0.294, p < 0.0001), WC (r = −0.294, p < 0.0001), %BF (r = −0.122, p = 0.028), WHR (r = −0.143, p = 0.009), triglycerides (r = −0.141, p = 0.011), HOMA-IR (r = −0.145, p = 0.027) and insulin (r = −0.130, p = 0.048). Leptin positively correlated with BMI (r = 0.628), WC (r = 0.530), BF% (r = 0.720), (all p < 0.0001); with DBP (r = 0.112, p = 0.043), total cholesterol (r = 0.324, p < 0.0001), LDL-cholesterol (r = 0.298, p < 0.0001), insulin (r = 0.320, p < 0.001 and HOMA-IR (r = 0.272, p < 0.0001).In multiple stepwise regression analysis, adiponectin was negatively associated with WC (β = −0.38, p = 0.001) and BF% (β = 0.33, p < 0.0001), while leptin was positively associated with BF% (β = 0.60, p < 0.0001), total cholesterol (β = 0.11, p = 0.02) and HOMA-IR (β = 0.11, p = 0.02). When controlled for gender, HOMA-IR was found significantly associated to adiponectin (β = 0.13, p = 0.046), but not BF%, while the association previously found between leptin and HOMA-IR disappeared; BMI and WC were significantly associated with leptin (β = 0.18, p = 0.04 & β = 0.19, p = 0.02 respectively).ConclusionThis study, which includes a population who was not receiving potentially confounding medications, confirms the associations previously observed of adiponectin with reduced adiposity especially central adiposity and improved insulin sensitivity. Confirmatory associations were also observed between leptin and obesity, blood lipids and insulin resistance for the first time in an African population. Gender was significant covariate interacting with insulin sensitivity/insulin resistance and obesity indexes associations in this population.

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“…PPARγ is a member of the nuclear receptor superfamily involved in estrogen-based protection of the cardiovascular and renal systems (62, 63). PPARγ is also closely linked to cardiovascular and metabolic dysfunction and therefore has the potential for being targeted by HLU which induces cardiovascular changes similar to aging or menopause (64). Considering the role of PPARγ in the regulation of vasodilation, vascular redox state, bioavailability of nitric oxide, as well as regulation of VSMC stiffness (65), our data implies that lower PPARγ may result in reduced protection against arterial stiffness caused by the exposure to HLU.…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Cardiovascular Adaptations to Simulated Microgravity in Sprague-Dawley Rats

Elsangeedy,

Yamaleyeva,

Edenhoffer

et al. 2024

Preprint

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Men and women have different cardiovascular responses to spaceflight; however few studies have focused on direct comparisons between sexes. Therefore, we investigated cardiovascular system differences, including arterial stiffness between socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) - an analogue for spaceflight-induced microgravity. Two weeks of HLU had no effect on body weight in either male or female rats. The index of arterial stiffness determined by ultrasound, pulse wave velocity (PWV), was greater in the aortic arch and carotid artery of females after HLU versus control females. HLU had no effect on arterial PWV in males. α smooth muscle actin, myosin, collagen, elastin, and collagen-to-elastin ratio were not different in rats of either sex in response to HLU. HLU exposure did not alter individual collagen fiber characteristics in studied groups. The levels of G protein-coupled estrogen receptor (GPER) were lower in the aorta of SD females exposed to HLU compared with female controls but not in males. These changes were associated with lower PPAR γ and increased oxidative stress markers (8-hydroxy-2’-deoxyguanosine and p47phox) in the females. Diastolic cardiac function was altered in females after HLU versus control females. GPER agonist, G1 prevented the increase in pulse wave velocity and 8-hydroxy-2’-deoxyguanosine, without altering PPAR γ or p47phox. Our data revealed that lower GPER in the HLU females contributes to the development of arterial stiffness, and that the SD rat is a suitable model to study the cardiovascular response of females to HLU.

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Sex hormones influence expression and function of peroxisome proliferator-activated receptor γ in adipocytes: pathophysiological aspects

Cited by 11 publications

References 49 publications

Increased adiposity, inflammation, metabolic disruption and dyslipidemia in adult male offspring of DOSS treated C57BL/6 dams

Increased adiposity, inflammation, metabolic disruption and dyslipidemia in adult male offspring of DOSS treated C57BL/6 dams

Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population

Sex-Specific Cardiovascular Adaptations to Simulated Microgravity in Sprague-Dawley Rats

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