Endocrinology and Metabolism

Original Articles

Diabetes, Obesity and Metabolism
Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat: Sun Ok Song, You-Cheol Hwang, Han Uk Ryu, Steven E. Kahn, Donna L. Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko; Endocrinol Metab. 2021;36(4):835-844. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1130

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Background
Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.
Methods
All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.
Results
A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm² in men and 63.1±39.5 cm² in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.
Conclusion
These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

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Fenofibrate add-on to statin treatment is associated with low all-cause death and cardiovascular disease in the general population with high triglyceride levels
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Metabolism.2022; 137: 155327. CrossRef
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Bo Gao, Xiangrui Li, Wenqing Chen, Shu’an Wang, Jian He, Yu Liu, Chao Ding, Xiaotian Chen
Lipids in Health and Disease.2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism: Ju Hee Lee, Saet-Byel Jung, Seong Eun Lee, Ji Eun Kim, Jung Tae Kim, Yea Eun Kang, Seul Gi Kang, Hyon-Seung Yi, Young Bok Ko, Ki Hwan Lee, Bon Jeong Ku, Minho Shong, Hyun Jin Kim; Endocrinol Metab. 2021;36(3):661-671. Published online June 22, 2021; DOI: https://doi.org/10.3803/EnM.2021.1023

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Background
The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPR^mt) in adipose tissue is associated with obesity in humans and rodents.
Methods
Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data.
Results
In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression.
Conclusion
Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

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Muchen Wu, Jing Wu, Kai Liu, Minjie Jiang, Fang Xie, Xuehong Yin, Jushan Wu, Qinghua Meng
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Jiangnan Zhang, Wenliang Qiao, Youfu Luo
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Ekaterina Sergeeva, Tatiana Ruksha, Yulia Fefelova
International Journal of Molecular Sciences.2023; 24(11): 9601. CrossRef
Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity
Natalia Todosenko, Olga Khaziakhmatova, Vladimir Malashchenko, Kristina Yurova, Maria Bograya, Maria Beletskaya, Maria Vulf, Natalia Gazatova, Larisa Litvinova
International Journal of Molecular Sciences.2023; 24(15): 12012. CrossRef
Down‐regulation of Lon protease 1 lysine crotonylation aggravates mitochondrial dysfunction in polycystic ovary syndrome
Yuan Xie, Shuwen Chen, Zaixin Guo, Ying Tian, Xinyu Hong, Penghui Feng, Qiu Xie, Qi Yu
MedComm.2023;[Epub] CrossRef
The mitochondrial unfolded protein response: A multitasking giant in the fight against human diseases
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Review Article

Obesity and Metabolism
Genetic and Environmental Factors Contributing to Visceral Adiposity in Asian Populations: Rachel Williams, Muthu Periasamy; Endocrinol Metab. 2020;35(4):681-695. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.772

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Obesity-associated metabolic illnesses are increasing at an alarming rate in Asian countries. A common feature observed in the Asian population is a higher incidence of abdominal obesity—the “skinny-fat” Asian syndrome. In this review, we critically evaluate the relative roles of genetics and environmental factors on fat distribution in Asian populations. While there is an upward trend in obesity among most Asian countries, it appears particularly conspicuous in Malaysia. We propose a novel theory, the Malaysian gene-environment multiplier hypothesis, which explains how ancestral variations in feast-and-famine cycles contribute to inherited genetic predispositions that, when acted on by modern-day stressors—most notably, urbanization, westernization, lifestyle changes, dietary transitions, cultural pressures, and stress—contribute to increased visceral adiposity in Asian populations. At present, the major determinants contributing to visceral adiposity in Asians are far from conclusive, but we seek to highlight critical areas for further research.

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Original Articles

Clinical Study
Apolipoprotein B Levels Predict Future Development of Hypertension Independent of Visceral Adiposity and Insulin Sensitivity: Seung Jin Han, Wilfred Y. Fujimoto, Steven E. Kahn, Donna L. Leonetti, Edward J. Boyko; Endocrinol Metab. 2020;35(2):351-358. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.351

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Background
High plasma apolipoprotein B (apoB) levels have been shown to be associated with hypertension, central obesity, and insulin resistance in cross-sectional research. However, it is unclear whether apoB levels predict future hypertension independent of body composition and insulin sensitivity. Therefore, we prospectively investigated whether plasma apoB concentrations independently predicted the risk of hypertension in a cohort of Japanese Americans.
Methods
A total of 233 normotensive Japanese Americans (77 men, 156 women; mean age, 46.4±11.0 years) were followed over 10 years to monitor them for the development of hypertension. Fasting plasma concentrations of apoB, glucose, and insulin were measured at baseline. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). The abdominal visceral and subcutaneous fat areas were measured at baseline using computed tomography. Logistic regression analysis was used to estimate the association between apoB concentrations and the odds of incident hypertension.
Results
The 10-year cumulative incidence of hypertension was 21.5%. The baseline apoB level was found to be positively associated with the odds of incident hypertension over 10 years after adjustment for age, sex, body mass index, systolic blood pressure, abdominal visceral fat area, abdominal subcutaneous fat area, total plasma cholesterol concentration, diabetes status, and HOMA-IR at baseline (odds ratio and 95% confidence interval for a 1-standard deviation increase, 1.89 [1.06 to 3.37]; P=0.030).
Conclusion
Higher apoB concentrations predicted greater risks of future hypertension independent of abdominal visceral fat area and insulin sensitivity in Japanese Americans.

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John Alvin, Damodara Gowda KM
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Clinical Study
Visceral-to-Subcutaneous Abdominal Fat Ratio Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis: Chan-Hee Jung, Eun-Jung Rhee, Hyemi Kwon, Yoosoo Chang, Seungho Ryu, Won-Young Lee; Endocrinol Metab. 2020;35(1):165-176. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.165

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Background

We evaluated the association of visceral-to-subcutaneous fat ratio (VSR) with nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis degree based on noninvasive serum fibrosis markers in the general population with NAFLD.

Methods

This is a cross-sectional study, in 7,465 Korean adults who underwent health screening examinations. NAFLD was defined as fatty liver detected on ultrasonography, and visceral and subcutaneous abdominal fat was measured using computed tomography. We predicted fibrosis based on the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI) and categorized the risk for advanced fibrosis as low, indeterminate, or high.

Results

The multivariable-adjusted prevalence ratios for indeterminate to high risk of advanced fibrosis based on FIB-4, determined by comparing the second, third, and fourth quartiles with the first quartile of VSR, were 3.38 (95% confidence interval [CI], 0.64 to 17.97), 9.41 (95% CI, 1.97 to 45.01), and 19.34 (95% CI, 4.06 to 92.18), respectively. The multivariable-adjusted prevalence ratios for intermediate to high degree of fibrosis according to APRI also increased across VSR quartiles (5.04 [95% CI, 2.65 to 9.59], 7.51 [95% CI, 3.91 to 14.42], and 19.55 [95% CI, 9.97 to 38.34], respectively). High VSR was more strongly associated with the prevalence of NAFLD in nonobese subjects than in obese subjects, and the associations between VSR and intermediate to high probability of advanced fibrosis in NAFLD were stronger in obese subjects than in nonobese subjects.

Conclusion

High VSR values predicted increased NAFLD risk and advanced fibrosis risk with NAFLD, and the predictive value of VSR for indeterminate to high risk of advanced fibrosis was higher in obese subjects than in nonobese subjects.

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Review Article

Bone Metabolism
Dual-Energy X-Ray Absorptiometry: Beyond Bone Mineral Density Determination: Yong Jun Choi; Endocrinol Metab. 2016;31(1):25-30. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.25

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Abstract PDF PubReader

Significant improvements in dual-energy X-ray absorptiometry (DXA) concerning quality, image resolution and image acquisition time have allowed the development of various functions. DXA can evaluate bone quality by indirect analysis of micro- and macro-architecture of the bone, which and improve the prediction of fracture risk. DXA can also detect existing fractures, such as vertebral fractures or atypical femur fractures, without additional radiologic imaging and radiation exposure. Moreover, it can assess the metabolic status by the measurement of body composition parameters like muscle mass and visceral fat. Although more studies are required to validate and clinically use these parameters, it is clear that DXA is not just for bone mineral densitometry.

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