Leptin is associated with vascular endothelial function in overweight patients with type 2 diabetes

Morioka, Tomoaki; Emoto, Masanori; Yamazaki, Yuko; Kawano, Naoya; Imamura, Satoshi; Numaguchi, Ryutaro; Urata, Hiromi; Motoyama, Koka; Mori, Katsuhito; Fukumoto, Shinya; Koyama, Hidenori; Shoji, Tetsuo; Inaba, Masaaki

doi:10.1186/1475-2840-13-10

Cited by 40 publications

(45 citation statements)

References 47 publications

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“…Obesity is an important contributor to the development of Type 2 diabetes and cardiovascular diseases (2,15,17,44). Impairments in vascular function associated with obesity are attributable to concomitant systemic risk factors including hypertension, hyperlipidemia, hyperglycemia, hyperinsulinemia, inflammatory cytokines, and sympathetic overactivity (5,20,25,27,40,41). Notably, there is evidence that obesityrelated endothelial dysfunction and structural changes are not homogenous throughout the arterial tree.…”

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confidence: 99%

Identification of genes whose expression is altered by obesity throughout the arterial tree

Padilla

Jenkins

Thorne

et al. 2014

Physiological Genomics

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We used next-generation RNA sequencing (RNA-Seq) technology on the whole transcriptome to identify genes whose expression is consistently affected by obesity across multiple arteries. Specifically, we examined transcriptional profiles of the iliac artery as well as the feed artery, first, second, and third branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats. Within the gastrocnemius and soleus muscles, the number of genes differentially expressed with obesity tended to increase with increasing branch order arteriole number (i.e., decreasing size of the artery). This trend was opposite in the diaphragm. We found a total of 15 genes that were consistently upregulated with obesity (MIS18A, CTRB1, FAM151B, FOLR2, PXMP4, OAS1B, SREBF2, KLRA17, SLC25A44, SNX10, SLFN3, MEF2BNB, IRF7, RAD23A, LGALS3BP) and five genes that were consistently downregulated with obesity (C2, GOLGA7, RIN3, PCP4, CYP2E1). A small fraction (ϳ9%) of the genes affected by obesity was modulated across all arteries examined. In conclusion, the present study identifies a select number of genes (i.e., 20 genes) whose expression is consistently altered throughout the arterial network in response to obesity and provides further insight into the heterogeneous vascular effects of obesity. Although there is no known direct function of the majority of 20 genes related to vascular health, the obesity-associated upregulation of SREBF2, LGALS3BP, IRF7, and FOLR2 across all arteries is suggestive of an unfavorable vascular phenotypic alteration with obesity. These data may serve as an important resource for identifying novel therapeutic targets against obesity-related vascular complications.next-generation sequencing; gene expression; resistance arteries; vascular dysfunction; OLETF rat model; Type 2 diabetes OVERNUTRITION AND LACK OF physical activity are the major triggers of the obesity epidemic in United States and worldwide (8 -10, 12, 39). Currently, one-third of Americans are obese (31), and according to projections this may reach 50% by 2030 (43). Obesity is an important contributor to the development of Type 2 diabetes and cardiovascular diseases (2,15,17,44). Impairments in vascular function associated with obesity are attributable to concomitant systemic risk factors including hypertension, hyperlipidemia, hyperglycemia, hyperinsulinemia, inflammatory cytokines, and sympathetic overactivity (5,20,25,27,40,41). Notably, there is evidence that obesityrelated endothelial dysfunction and structural changes are not homogenous throughout the arterial tree. For example, studies using the hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of obesity demonstrate that the soleus feed artery (SFA) is more resistant to impairments in vasomotor activity (6) as well as more resistant to increases in intimamedia thickness (21) compared with the gastrocnemius feed artery (GFA). A possible explanation for the fundamental differe...

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confidence: 99%

Identification of genes whose expression is altered by obesity throughout the arterial tree

Padilla

Jenkins

Thorne

et al. 2014

Physiological Genomics

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“…On the other hand, it is also reported that plasma adipocytokine levels such as leptin were positively associated with vascular endothelial function in overweight patients (Morioka et al 2014). Therefore, adipose tissue may have some influence on endothelial function.…”

Section: Limitations Of This Studymentioning

confidence: 93%

Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats

Serizawa¹,

Tashiro²,

Takeda

et al. 2015

Journal of Endocrinology

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Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20 ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARg) in femoral arteries and cultured endothelial cells. Although PPARg is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARg in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect of ELD might be exerted through improvement of endothelial nitric oxide synthase uncoupling, which is mediated by an antioxidative effect through normalization of vascular PPARg/NF-kB signaling.

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“…WC was measured to the nearest centimeter at the level of the umbilicus in a standing position at the end of gentle expiration. Blood was drawn after an overnight fast, and biochemical parameters were analyzed by a standard laboratory method as previously described 26) .…”

Section: Methodsmentioning

confidence: 99%

Visceral Adiposity is Preferentially Associated with Vascular Stiffness Rather than Thickness in Men with Type 2 Diabetes

Morigami

Morioka

Yamazaki

et al. 2016

JAT

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Aim: Visceral fat accumulation is known to underlie the clustering of cardiovascular risk factors. However, it is not completely understood how visceral fat accumulation influences the development of cardiovascular disease. In this study, we investigated the clinical impact of visceral adiposity on vascular stiffness and thickness in patients with type 2 diabetes (T2D).Methods: One hundred and sixty-one patients with T2D, including 92 men and 69 women, were included in this cross-sectional study. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by dual bioelectrical impedance analysis. Stiffness parameter β and intima-media thickness (IMT) of the common carotid artery were measured by ultrasonography.Results: The mean age and duration of diabetes in the study population were 61 years and 13.9 years, respectively. In men, VFA and waist circumference (WC) were positively correlated with stiffness parameter β, whereas body mass index (BMI), WC, and SFA were negatively correlated with IMT. In contrast, in women, none of the obesity-related indices were significantly correlated with stiffness parameter β or IMT. In multiple regression analyses, VFA as well as WC, BMI, and SFA were independently associated with stiffness parameter β after adjustment for age and other potential confounders in men but not in women. None of the obesity-related indices were independently associated with IMT for either sex.Conclusion: In men with T2D, visceral adiposity is associated with carotid arterial stiffness but not thickness.

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Leptin is associated with vascular endothelial function in overweight patients with type 2 diabetes

Cited by 40 publications

References 47 publications

Identification of genes whose expression is altered by obesity throughout the arterial tree

Identification of genes whose expression is altered by obesity throughout the arterial tree

Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats

Visceral Adiposity is Preferentially Associated with Vascular Stiffness Rather than Thickness in Men with Type 2 Diabetes

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