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Ectopic Fat Continuum: New Concept Based on Clinical and Basic Evidence

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 11507

Special Issue Editor

Dr. Michio Shimabukuro

E-Mail Website
Guest Editor
Department of Diabetes, Endocrinology and Metabolism, Fukushima Medical University, Fukushima 960-1295, Japan
Interests: cardiovascular disease; ectopic fat; obesity disease; visceral fat; insulin resistance; diabetes mellitus; lipotoxicity; cardiometabolic disease; sex differences; epicardial fat

Special Issue Information

Dear Colleagues,

A growing body of evidence is indicating the pathophysiological role of fat depots in non-adipose organs. Ectopic fat depots within liver, skeletal muscle, kidney, and pancreatic β cells, as well as around heart and blood vessels, can be more strongly associated with cardiometabolic risk than classical adiposity variables such as body mass index. Upon ectopic fat depots, the intracellular accumulation of free fatty acids promotes ER (endoplasmic reticulum) stress, mitochondrial uncoupling, oxidative stress, and metabolic derangements, finally promoting inflammatory response and cell apoptosis and/or death. Ectopic fat depots are obviously related to obesity, but can be more largely related to visceral fat depots which reflect particularly dysfunctional subcutaneous adipose tissue. It is likely that ectopic fat depots have local effects with relevant clinical consequences.

This Special Issue of the Journal of Clinical Medicine will cover the following important aspects of ectopic fat continuum in clinical and basic research.

Ectopic fat depots, body composition, visceral fat obesity, metabolic syndrome, and diabetes mellitus;

Ectopic fat depots in pancreatic β cells and skeletal muscle, and modulations of insulin secretion and insulin resistance;

Epicardial and cardiac fat and cardiovascular diseases such as atherosclerotic cardiovascular diseases (ASCVDs), hypertension, left-ventricular dysfunction, heart failure (HFrEF and HfpEF), atrial fibrillation, and other arrhythmia;

Ectopic fat depots and nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and liver cancer;

Ectopic fat depots in the kidney  (pararenal and renal sinus fat) and chronic kidney disease;

Ectopic fat depots and risk stratification for onset of diabetes and cardiovascular risk.

Dr. Michio Shimabukuro
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ectopic fat
  • obesity disease
  • visceral fat
  • insulin resistance
  • diabetes mellitus
  • lipotoxicity
  • cardiometabolic disease
  • sex differences
  • epicardial fat

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Published Papers (4 papers)

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Research

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15 pages, 2411 KiB  
Article
Development and Internal Validation of Fatty Liver Prediction Models in Obese Children and Adolescents
by Giorgio Bedogni, Sofia Tamini, Diana Caroli, Sabrina Cicolini, Marco Domenicali and Alessandro Sartorio
J. Clin. Med. 2021, 10(7), 1470; https://doi.org/10.3390/jcm10071470 - 2 Apr 2021
Cited by 6 | Viewed by 1980
Abstract
To develop predictive models of fatty liver (FL), we performed a cross-sectional retrospective study of 1672 obese children with a median (interquartile range) age of 15 (13–16) years. The outcome variable was FL diagnosed by ultrasonography. The potential predictors were: (1) binary: sex; [...] Read more.
To develop predictive models of fatty liver (FL), we performed a cross-sectional retrospective study of 1672 obese children with a median (interquartile range) age of 15 (13–16) years. The outcome variable was FL diagnosed by ultrasonography. The potential predictors were: (1) binary: sex; (2) continuous: age, body mass index (BMI), waist circumference (WC), alanine transaminase (ALT), aspartate transaminase, gamma-glutamyltransferase, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), HDL-cholesterol, LDL-cholesterol, triglycerides, mean arterial pressure, uric acid, and c-reactive protein; (3) ordinal: Pubertal status. Bootstrapped multivariable logistic regression with fractional polynomials was used to develop the models. Two models were developed and internally validated, one using BMI and the other using WC as the anthropometric predictor. Both models included ALT, HOMA-IR, triglycerides, and uric acid as predictors, had similar discrimination (c-statistic = 0.81), and were similarly well calibrated as determined by calibration plots. These models should undergo external validation before being employed in clinical or research practice. Full article
(This article belongs to the Special Issue Ectopic Fat Continuum: New Concept Based on Clinical and Basic Evidence)
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12 pages, 2012 KiB  
Article
Endurance Runners with Intramyocellular Lipid Accumulation and High Insulin Sensitivity Have Enhanced Expression of Genes Related to Lipid Metabolism in Muscle
by Saori Kakehi, Yoshifumi Tamura, Kageumi Takeno, Shin-ichi Ikeda, Yuji Ogura, Norio Saga, Takeshi Miyatsuka, Hisashi Naito, Ryuzo Kawamori and Hirotaka Watada
J. Clin. Med. 2020, 9(12), 3951; https://doi.org/10.3390/jcm9123951 - 6 Dec 2020
Cited by 3 | Viewed by 2427
Abstract
Context: Endurance-trained athletes have high oxidative capacities, enhanced insulin sensitivities, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. Design and setting: We compared intramyocellular lipid (IMCL), insulin sensitivity, and gene expression levels [...] Read more.
Context: Endurance-trained athletes have high oxidative capacities, enhanced insulin sensitivities, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. Design and setting: We compared intramyocellular lipid (IMCL), insulin sensitivity, and gene expression levels of the muscle in eight nonobese healthy men (control group) and seven male endurance athletes (athlete group). Their IMCL levels were measured by proton-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by glucose infusion rate (GIR) during a euglycemic–hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR (qRT-PCR) and microarray analysis. Results: IMCL levels in the tibialis anterior muscle were approximately 2.5 times higher in the athlete group compared to the control group, while the IMCL levels in the soleus muscle and GIR were comparable. In the microarray hierarchical clustering analysis, gene expression patterns were not clearly divided into control and athlete groups. In a gene set enrichment analysis with Gene Ontology gene sets, “RESPONSE TO LIPID” was significantly upregulated in the athlete group compared with the control group. Indeed, qRT-PCR analysis revealed that, compared to the control group, the athlete group had 2–3 times higher expressions of proliferator-activated receptor gamma coactivator-1 alpha (PGC1A), adiponectin receptors (AdipoRs), and fatty acid transporters including fatty acid transporter-1, plasma membrane-associated fatty acid binding protein, and lipoprotein lipase. Conclusions: Endurance runners with higher IMCL levels have higher expression levels of genes related to lipid metabolism such as PGC1A, AdipoRs, and fatty acid transporters in muscle. Full article
(This article belongs to the Special Issue Ectopic Fat Continuum: New Concept Based on Clinical and Basic Evidence)
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15 pages, 1408 KiB  
Article
CD36 and GPR120 Methylation Associates with Orosensory Detection Thresholds for Fat and Bitter in Algerian Young Obese Children
by Moustafa Berrichi, Aziz Hichami, Lynda Addou-Klouche, Amira Sayed Khan and Naim Akhtar Khan
J. Clin. Med. 2020, 9(6), 1956; https://doi.org/10.3390/jcm9061956 - 23 Jun 2020
Cited by 9 | Viewed by 2728
Abstract
Background: The spontaneous preference for dietary fat is regulated by two lingual lipid sensors (CD36 and GPR120) in humans and rodents. Our objective was to investigate whether obesity in children is associated with methylation of lipid sensor genes, and whether this [...] Read more.
Background: The spontaneous preference for dietary fat is regulated by two lingual lipid sensors (CD36 and GPR120) in humans and rodents. Our objective was to investigate whether obesity in children is associated with methylation of lipid sensor genes, and whether this alteration was implicated in altered gustatory perception of fat and bitter and increased preference of palatable foods. Methods: School children were recruited and classified according to their body mass index (BMI) z-score into two groups: obese and lean children. The detection of orosensory perception for oleic acid and 6-n-propylthiouracil was assessed by using a 3-alternative forced-choice test. After blood DNA extraction, methylation patterns were investigated by methylation-specific PCR. The children were also subjected to a food habit questionnaire. Results: Obese children showed higher lipid and bitter detection thresholds than lean children. Besides, more obese children presented higher methylation level of the CpG sites than lean participants. Interestingly, CD36 and GPR120 gene methylation was associated with high lipid detection thresholds in obese participants. The obese participants preferred highly palatable fat-rich food items, associated with CD36 and GPR120 gene methylation. Conclusion: Epigenetic changes in CD36 and GPR120 genes might contribute to low orosensory perception of fat and bitter taste, and might be, consequently, critically involved in obesity in children Full article
(This article belongs to the Special Issue Ectopic Fat Continuum: New Concept Based on Clinical and Basic Evidence)
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Review

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7 pages, 3473 KiB  
Review
Ectopic Fat Accumulation in Pancreas and Heart
by Junji Kozawa and Iichiro Shimomura
J. Clin. Med. 2021, 10(6), 1326; https://doi.org/10.3390/jcm10061326 - 23 Mar 2021
Cited by 18 | Viewed by 3752
Abstract
Ectopic fat is found in liver, muscle, and kidney and is known to accumulate as visceral fat. In recent years, ectopic fat has also been observed in the pancreas, and it has been said that pancreatic fat accumulation is related to the pathophysiology [...] Read more.
Ectopic fat is found in liver, muscle, and kidney and is known to accumulate as visceral fat. In recent years, ectopic fat has also been observed in the pancreas, and it has been said that pancreatic fat accumulation is related to the pathophysiology of diabetes and the onset of diabetes, but the relationship has not yet been determined. In the heart, epicardium fat is another ectopic fat, which is associated with the development of coronary artery disease. Ectopic fat is also observed in the myocardium, and diabetic patients have more fat accumulation in this tissue than nondiabetic patients. Myocardium fat is reported to be related to diastolic cardiac dysfunction, which is one of the characteristics of the complications observed in diabetic patients. We recently reported that ectopic fat accumulation was observed in coronary arteries of a type 2 diabetic patient with intractable coronary artery disease, and coronary artery is attracting attention as a new tissue of ectopic fat accumulation. Here, we summarize the latest findings focusing on the relationship between ectopic fat accumulation in these organs and diabetic pathophysiology and complications, then describe the possibility of future treatments targeting these ectopic fat accumulations. Full article
(This article belongs to the Special Issue Ectopic Fat Continuum: New Concept Based on Clinical and Basic Evidence)
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