Ectopic fat deposition and global cardiometabolic risk: New paradigm in cardiovascular medicine

Shimabukuro, Michio; Kozuka, Chisayo; Taira, Shinichiro; Yabiku, Koichi; Dagvasumberel, Munkhbaatar; Ishida, Masaharu; Matsumoto, Sachiko; Yagi, Shusuke; Fukuda, Daiju; Yamakawa, Ken; Higa, Moritake; Soeki, Takeshi; Yoshida, Hisashi; Masuzaki, Hiroaki; Sata, Masataka

doi:10.2152/jmi.60.1

Cited by 63 publications

(58 citation statements)

References 81 publications

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“…Visceral fat is strongly related to the development of cardiovascular diseases [17] and, generally, an increase in visceral fat is accompanied by overall weight gain. In some cases visceral fat can be increased without overall weight gain.…”

Section: Discussionmentioning

confidence: 99%

Can increased visceral adiposity without body weight changes accelerate carotid atherosclerosis in South Korean participants with type 2 diabetes?

Kim

Araneta

et al. 2015

Journal of Diabetes and its Complications

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Aims: Type 2 diabetes mellitus (T2DM) and visceral obesity are associated with each other and with cardiovascular diseases. We determined whether increased visceral adiposity without weight gain was associated with sex-specific accelerated carotid atherosclerosis in South Koreans with T2DM. Methods: From 2003 to 2012, we recruited 280 participants with T2DM for the Seoul Metabolic Syndrome cohort who had body weight, visceral fat thickness (VFT), and carotid intima-media thickness (CIMT) measured at intervals of 2 years. According to VFT change, sex-specific quartiles of clinical characteristics and changes of CIMT were determined. Logistic regression models predicted the odds of the progression of CIMTs in each quartile. Results: During 2 years of observation, VFTs fell by 5.2±13.5 mm in men (P<0.001) and 3.4±10.5 mm in women (P<0.001). Progression of IMT was only significant for women's maximal IMT (0.031±0.145 mm, P=0.012), while significant improvements in HbA1c were found (0.9%; P<0.001 in both sexes). There were no significant differences in clinical characteristics, or in progression of carotid IMT in men or women according to 2-year quartiles of VFT change. Conclusions: Our results do not suggest that increased visceral adiposity without body weight changes impacts the CIMT progression in South Korean men or women with T2DM. Thank you for the opportunity to revise again, based on the helpful critique of Reviewer 1. Please see our specific responses to reviewers' comments below.Reviewer #1: In this study, they have reported that visceral obesity leads to atherosclerosis. Ultrasonography is a noninvasive, cost-effective method to assess visceral obesity. Visceral fat change without weight change had little effect on atherosclerosis. Despite the advantages, use of sonography for assessment of body composition is accompanied by important disadvantages. Sonography entails use of equipment and is significantly more expensive than simple assessment of anthropometric features. Although the value of sonography has been shown in most studies, sporadic reports question the strong association between sonographic findings and those of standard techniques [1] and clinical outcome [2]. There is also an evident need for objective and accurate indexes such as intraabdominal fat thickness, abdominal wall fat index, preperitoneal fat, minimum subcutaneous fat thickness, mesenteric fat thickness and preperitoneal circumference that can be applied to special patient groups. Furthermore, adequate examiner training is demanded as a precondition for reliable and reproducible measurements. Once these issues are resolved, it is highly plausible that sonography will be used in clinical practice for the routine assessment of regional adiposity. Therefore in my opinion regional adiposity can be assessed with anthropometric data and imaging techniques. The former include waist-to-hip ratio, waist circumference, and abdominal sagittal diameter. A fully automated individualized analyses method is now possible and may, given a...

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Section: Discussionmentioning

confidence: 99%

Can increased visceral adiposity without body weight changes accelerate carotid atherosclerosis in South Korean participants with type 2 diabetes?

Kim

Araneta

et al. 2015

Journal of Diabetes and its Complications

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“…In other words, ectopic deposition of fat e.g. in skeletal muscle or liver is per se associated with an increased metabolic risk (Shimabukuro et al, 2013). This is best exemplified in patients suffering from lipodystrophy who are unable to store fat in white adipose tissue.…”

Section: Adipose Tissue and Adipokinesmentioning

confidence: 99%

Translational value of animal models of obesity—Focus on dogs and cats

Osto

Lutz

2015

European Journal of Pharmacology

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A prolonged imbalance between a relative increase in energy intake over a decrease in energy expenditure results in the development of obesity; extended periods of a positive energy balance eventually lead to the accumulation of abnormally high amounts of fat in adipose tissue but also in other organs. Obesity is considered a clinical state of impaired general heath in which the excessive increase in adipose tissue mass may be associated with metabolic disorders such as type 2 diabetes mellitus, hyperlipidemia, hypertension and cardiovascular diseases. This review discusses briefly the use of animal models for the study of obesity and its comorbidities. Generally, most studies are performed with rodents, such as diet induced obesity and genetic models. Here, we focus specifically on two different species, namely dogs and cats. Obese dogs and cats show many features of human obesity. Interestingly, however, dogs and cats differ from each other in certain aspects because even though obese dogs may become insulin resistant, this does not result in the development of diabetes mellitus. In fact, diabetes in dogs is typically not associated with obesity because dogs present a type 1 diabetes-like syndrome. On the other hand, obese cats often develop diabetes mellitus which shares many features with human type 2 diabetes; feline and human diabetes are similar in respect to their pathophysiology, underlying risk factors and treatment strategies. Our review discusses genetic and endocrine factors in obesity, discusses obesity induced changes in lipid metabolism and includes some recent findings on the role of gut microbiota in obesity. Compared to research in rodent models, the array of available techniques and tools is unfortunately still rather limited in dogs and cats. Hence, even though physiological and pathophysiological phenomena are well described in dogs and cats, the underlying mechanisms are often not known and studies investigating causality specifically are scarce. diabetes; feline and human diabetes are similar in respect to their pathophysiology, underlying risk factors and treatment strategies. Our review discusses genetic and endocrine factors in obesity, discusses obesity induced changes in lipid metabolism and includes some recent findings on the role of gut microbiota in obesity. Compared to research in rodent models, the array of available techniques and tools is unfortunately still rather limited in dogs and cats.Hence, even though physiological and pathophysiological phenomena are well described in dogs and cats, the underlying mechanisms are often not known and studies investigating causality specifically are scarce.

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“…A number of recent studies demonstrated that PAT affect the functions of PAT-adjacent vasculature and contribute to vascular remodeling. 46,47 Adipocytes originally differentiate from adipocyte progenitors and are related to the remodeling of adipose tissues under certain local and general conditions. MSCs residing in the perivascular region depots form and give rise to resident adipocyte progenitors.…”

Section: Mpcs Exhibit Bipotential Pluripotencymentioning

confidence: 99%

Immortalized multipotent pericytes derived from the vasa vasorum in the injured vasculature. A cellular tool for studies of vascular remodeling and regeneration

Kabara

Kawabe

Matsuki

et al. 2014

Laboratory Investigation

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Adventitial microvessels, vasa vasorum in the vessel walls, have an active role in the vascular remodeling, although its mechanisms are still unclear. It has been reported that microvascular pericytes (PCs) possess mesenchymal plasticity. Therefore, microvessels would serve as a systemic reservoir of stem cells and contribute to the tissues remodeling. However, most aspects of the biology of multipotent PCs (mPCs), in particular of pathological microvessels are still obscure because of the lack of appropriate methods to detect and isolate these cells. In order to examine the characteristics of mPCs, we established immortalized cells residing in adventitial capillary growing at the injured vascular walls. We recently developed in vivo angiogenesis to observe adventitial microvessels using collagen-coated tube (CCT), which also can be used as an adventitial microvessel-rich tissue. By using the CCT, CD146-or NG2-positive cells were isolated from the adventitial microvessels in the injured arteries of mice harboring a temperature-sensitive SV40 T-antigen gene. Several capillary-derived endothelial cells (cECs) and PCs (cPCs) cell lines were established. cECs and cPCs maintain a number of key endothelial and PC features. Co-incubation of cPCs with cECs formed capillary-like structure in Matrigel. Three out of six cPC lines, termed capillary mPCs demonstrated both mesenchymal stem cell-and neuronal stem cell-like phenotypes, differentiating effectively into adipocytes, osteoblasts, as well as schwann cells. mPCs differentiated to ECs and PCs, and formed capillary-like structure on their own. Transplanted DsRed-expressing mPCs were resident in the capillary and muscle fibers and promoted angiogenesis and myogenesis in damaged skeletal muscle. Adventitial mPCs possess transdifferentiation potential with unique phenotypes, including the reconstitution of capillary-like structures. Their phenotype would contribute to the pathological angiogenesis associated with vascular remodeling. These cell lines also provide a reproducible cellular tool for high-throughput studies on angiogenesis, vascular remodeling, and regeneration as well.

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Ectopic fat deposition and global cardiometabolic risk: New paradigm in cardiovascular medicine

Cited by 63 publications

References 81 publications

Can increased visceral adiposity without body weight changes accelerate carotid atherosclerosis in South Korean participants with type 2 diabetes?

Can increased visceral adiposity without body weight changes accelerate carotid atherosclerosis in South Korean participants with type 2 diabetes?

Translational value of animal models of obesity—Focus on dogs and cats

Immortalized multipotent pericytes derived from the vasa vasorum in the injured vasculature. A cellular tool for studies of vascular remodeling and regeneration

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