Maintenance of Subcutaneous Fat Homeostasis Improves Systemic Metabolic Dysfunction in Obesity

Shimizu, Ippei; Yoshida, Yohko; Minamino, Tohru

doi:10.2337/dbi15-0013

Cited by 14 publications

(11 citation statements)

References 17 publications

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“…It was also found that visceral but not subcutaneous fat was associated with increasing levels of C-reactive protein and TNFα 53 . Although the reason why subcutaneous fat is less prone to develop inflammation is unclear yet, one possible explanation is due to the protein inhibitor of activated STAT 1 (PIAS1) which is highly expressed in subcutaneous fat depot 54 , 55 . It was found that PIAS1 suppressed the inflammation in subcutaneous fat via inactivation of c-Jun N-terminal kinase 54 , 55 .…”

Section: Discussionmentioning

confidence: 99%

“…Although the reason why subcutaneous fat is less prone to develop inflammation is unclear yet, one possible explanation is due to the protein inhibitor of activated STAT 1 (PIAS1) which is highly expressed in subcutaneous fat depot 54 , 55 . It was found that PIAS1 suppressed the inflammation in subcutaneous fat via inactivation of c-Jun N-terminal kinase 54 , 55 . These mechanisms might provide explanations to the benefits of the expansion of subcutaneous fat caused by physiologically-relevant HFD-induced FGF21 although browning of SAT is not affected.…”

Section: Discussionmentioning

confidence: 99%

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Fibroblast growth factor 21 increases insulin sensitivity through specific expansion of subcutaneous fat

et al. 2018

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Although the pharmacological effects of fibroblast growth factor 21 (FGF21) are well-documented, uncertainty about its role in regulating excessive energy intake remains. Here, we show that FGF21 improves systemic insulin sensitivity by promoting the healthy expansion of subcutaneous adipose tissue (SAT). Serum FGF21 levels positively correlate with the SAT area in insulin-sensitive obese individuals. FGF21 knockout mice (FGF21KO) show less SAT mass and are more insulin-resistant when fed a high-fat diet. Replenishment of recombinant FGF21 to a level equivalent to that in obesity restores SAT mass and reverses insulin resistance in FGF21KO, but not in adipose-specific βklotho knockout mice. Moreover, transplantation of SAT from wild-type to FGF21KO mice improves insulin sensitivity in the recipients. Mechanistically, circulating FGF21 upregulates adiponectin in SAT, accompanied by an increase of M2 macrophage polarization. We propose that elevated levels of endogenous FGF21 in obesity serve as a defense mechanism to protect against systemic insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 21 increases insulin sensitivity through specific expansion of subcutaneous fat

et al. 2018

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“…There is heterogeneity among previous studies assessing the relationship between BMI and CVD [101112]. This heterogeneity might be due to the limitations in defining obesity based on BMI [11920212223242526]. BMI cannot accurately distinguish fat, bone, and muscle mass; therefore, it cannot effectively estimate the total body fat mass [19].…”

Section: Discussionmentioning

confidence: 99%

The Association between Z-Score of Log-Transformed A Body Shape Index and Cardiovascular Disease in Korea

et al. 2019

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BackgroundIn order to overcome the limitations of body mass index (BMI) and waist circumference (WC), the z-score of the log-transformed A Body Shape Index (LBSIZ) has recently been introduced. In this study, we analyzed the relationship between the LBSIZ and cardiovascular disease (CVD) in a Korean representative sample.MethodsData were collected from the Korea National Health and Nutrition Examination VI to V. The association between CVD and obesity indices was analyzed using a receiver operating characteristic curve. The cut-off value for the LBSIZ was estimated using the Youden index, and the odds ratio (OR) for CVD was determined via multivariate logistic regression analysis. ORs according to the LBSIZ value were analyzed using restricted cubic spline regression plots.ResultsA total of 31,227 Korean healthy adults were analyzed. Area under the curve (AUC) of LBSIZ against CVD was 0.686 (95% confidence interval [CI], 0.671 to 0.702), which was significantly higher than the AUC of BMI (0.583; 95% CI, 0.567 to 0.599) or WC (0.646; 95% CI, 0.631 to 0.661) (P<0.001). Similar results were observed for stroke and coronary artery diseases. The cut-off value for the LBSIZ was 0.35 (sensitivity, 64.5%; specificity, 64%; OR, 1.29, 95% CI, 1.12 to 1.49). Under restricted cubic spline regression, LBSIZ demonstrated that OR started to increase past the median value.ConclusionThe findings of this study suggest that the LBSIZ might be more strongly associated with CVD risks compared to BMI or WC. These outcomes would be helpful for CVD risk assessment in clinical settings, especially the cut-off value of the LBSIZ suggested in this study.

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“…Furthermore, the metabolic effects of fat differ according to its location. For example, excess visceral fat mass has deleterious effects on metabolism and is an independent risk factor of metabolic syndrome, type 2 diabetes, CVD and cancer [ 24 , 25 ], whereas subcutaneous fat has beneficial effects on metabolism [ 26 ]. In one animal study, subcutaneous fat transplantation improved metabolic dysfunction in an obese mouse model [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

The influence of physical activity on risk of cardiovascular disease in people who are obese but metabolically healthy

Moon

Choi

et al. 2017

PLoS ONE

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The metabolic outcomes of metabolically healthy obesity (MHO) remain controversial. The aim of the present study was to determine the effect of physical activity on the cardiovascular disease (CVD) outcomes of MHO. The study included participants who were followed for 10 years and recruited from the Korean Genome and Epidemiology Study (KoGES), a population-based cohort study. Participants with previously recorded CVDs or cancer, or who had received steroids or anticoagulants at baseline were excluded. A total of 8144 participants (3,942 men and 4,202 women) fulfilled inclusion criteria. In a multivariate Cox regression model adjusted for age and sex, MHO participants were not at elevated risk of CVD compared with their metabolically healthy non-obese (MHNO) counterparts (HR, 1.28; 95% CI, 0.96–1.71), although both the non-obese (HR, 1.50; 95% CI, 1.19–1.90) and obese (HR, 1.85; 95% CI, 1.48–2.30) participants with metabolic abnormalities were at elevated risk. However, in the subgroup analysis by physical activity, physically inactive MHO participants had a significantly higher HR for CVD events compared to active MHNO participants (HR, 1.54; 95% CI, 1.03–2.30), while active MHO participants were not at elevated risk (HR, 1.15; 95% CI, 0.70–1.89). Physically inactive MHO participants had significantly increased risk of CVD compared to physically active MHNO participants whereas physically active MHO participants did not.

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Maintenance of Subcutaneous Fat Homeostasis Improves Systemic Metabolic Dysfunction in Obesity

Cited by 14 publications

References 17 publications

Fibroblast growth factor 21 increases insulin sensitivity through specific expansion of subcutaneous fat

Fibroblast growth factor 21 increases insulin sensitivity through specific expansion of subcutaneous fat

The Association between Z-Score of Log-Transformed A Body Shape Index and Cardiovascular Disease in Korea

The influence of physical activity on risk of cardiovascular disease in people who are obese but metabolically healthy

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