Fatty Liver Has Stronger Association With Insulin Resistance Than Visceral Fat Accumulation in Nonobese Japanese Men

Kadowaki, Shigenori; Tamura, Yasuaki; Someya, Yuki; Takeno, Kageumi; Kaga, Hideyoshi; Kakehi, Saori; Fukushima, Takashi; Furukawa, Yasushi; Suzuki, Ruriko; Nishitani‐Yokoyama, Miho; Shimada, Kazunori; Daida, Hiroyuki; Aoki, Shigeki; Kanazawa, Akio; Kawamori, Ryuzo; Watada, Hirotaka

doi:10.1210/js.2019-00052

Cited by 23 publications

(21 citation statements)

References 31 publications

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“…In skeletal muscle with decreased mass or steatosis, the unused glucose is transported to the liver due to insulin resistance and synthesis of triglycerides progresses; thus, NAFLD develops. 24 Another problem is muscle steatosis. Muscle steatosis was similarly observed in the non-obese NAFLD and obese NAFLD groups and was markedly observed in women.…”

Section: Discussionmentioning

confidence: 99%

Clinical and anthropometric characteristics of non‐obese non‐alcoholic fatty liver disease subjects in Japan

Sugiyama

Oshida

Suzuki

et al. 2020

Hepatology Research

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Aim The underlying mechanism of non‐obese non‐alcoholic fatty liver disease (NAFLD) has not been fully elucidated. We classified patients with NAFLD by sex and body mass index and compared their clinical features to clarify the background pathophysiology of non‐obese NAFLD. Methods A total of 404 patients with NAFLD were divided according to their body mass index (<25 [non‐obese], 25 to <30 [obese], and ≥30 [severe obese]), and were further compared with 253 patients without obesity and NAFLD (non‐NAFLD). Results The proportion of the individuals with non‐obese NAFLD was 25.7% in men and 27.6% in women. The male and female non‐obese NAFLD groups had lower skeletal muscle mass and muscle strength than the obese NAFLD groups. The visceral fat area, although low, was ≥100 cm2 in 59.3% of men and 43.8% of women. An increase in liver fat accumulation, hepatic fibrosis, homeostasis model assessment of insulin resistance, and leptin levels was modest in the non‐obese NAFLD group compared with a marked increase in the obese NAFLD groups. The muscle mass of the non‐obese NAFLD group was similar to that of the non‐NAFLD group, but muscle steatosis was particularly common among women. Multivariate analysis revealed that the factors contributing to increased liver fat accumulation in the non‐obese NAFLD group were visceral fat area, HbA1c, myostatin, and leptin. Conclusions In patients with non‐obese NAFLD, a sex difference was observed in the clinical features. In addition to increased visceral fat, decreased muscle mass and muscle strength, muscle atrophy (presarcopenia), and impaired glucose tolerance were considered to be important pathophysiological factors.

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Section: Discussionmentioning

confidence: 99%

Clinical and anthropometric characteristics of non‐obese non‐alcoholic fatty liver disease subjects in Japan

Sugiyama

Oshida

Suzuki

et al. 2020

Hepatology Research

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“…FL was associated with adipose tissue and muscle insulin resistance; however, VFA alone were not associated with insulin resistance. Subjects with both VFA and FL were as resistant to insulin as those with FL alone [14].…”

Section: Introductionmentioning

confidence: 87%

“…In non-obese Asians, as in other ethnic groups, visceral fat accumulation (VFA) and fatty liver (FL) are reported to be associated with insulin resistance and metabolic abnormalities [8][9][10][11][12][13]. Metabolically obese, normal-weight Asians have 20-30% lesser insulin sensitivity and 30-40% higher fasting and postprandial insulin secretion than metabolically healthy, lean controls [14] Among Japanese men with BMI of 23-25 kg/m 2 , those with hypertension, hyperglycemia, or dyslipidemia have insulin resistance in the liver but less insulin resistance in the muscle. On the other hand, overweight men with metabolic syndrome have impaired insulin resistance in both the muscle and liver [4].…”

Section: Introductionmentioning

confidence: 99%

“…Based on these studies [14], we divided our study patients into four groups based on the accumulation of FL and visceral fat and with normal BMI (<25 kg/m 2 ) at the time of a medical checkup. We investigated clinically whether there was a difference in lifestyle-related diseases, blood test values, and liver fibrosis progression depending on the FL and VFA sites.…”

Section: Introductionmentioning

confidence: 99%

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Fatty Liver, and Not Visceral Fat, Is More Associated with Liver Fibrosis and Diabetes in Non-Obese Japanese Individuals: A Cross-Sectional Study

Urata

Kawanaka

Nishino

et al. 2020

Life

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Asians are known to be more likely than Westerners to develop fatty liver and lifestyle-related diseases in spite of their weight. However, the relationship between fat accumulation and lifestyle-related diseases in non-obese Asians is unknown. Therefore, this study aimed to analyze visceral fat and hepatic fat in participants with a normal body mass index (BMI) and examine their characteristics during a medical checkup. This cross-sectional study was conducted on 663 of 1142 patients who underwent abdominal ultrasonography and who had an alcohol intake (converted to ethanol) of <30 g/day for males and <20 g/day for females and a BMI of <25 kg/m2 during a health checkup. Participants were classified into four groups: group A, visceral fat accumulation (VFA) (−) and fatty liver (FL) (−) (n = 549); group B, VFA (+) and FL (−) (n = 32); group C, VFA (−) and FL (+) (n = 58); and group D, VFA (+) and FL (+) (n = 24). The frequencies of lifestyle-related disease complications, liver function tests, and liver fibrosis were evaluated among the four groups. Compared with group A (control), groups B, C, and D had a higher number of males, BMI, abdominal circumference, ALT, AST, γ-GTP, triglyceride, uric acid, fasting blood sugar levels, and incidence of hyperlipidemia. Groups C and D had higher ALT, HbA1c, cholinesterase, and triglyceride levels, FIB4 index, and the number of patients with diabetes mellitus (DM) than groups A and B; however, there was no difference between groups A and B. FL is a risk factor of DM and liver fibrosis in non-obese Japanese individuals; however, VFA only is not a risk factor of DM and liver fibrosis.

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“…Metabolic syndrome can be accompanied by fatty liver, visceral adiposity, muscular lipid accumulation (namely, ectopic fat accumulation), impaired insulin action via free fatty acids, micro-inflammation, and tissue-derived humoral factors (referred to as "adipokines" when they are from adipose tissue, "hepatokines" when they are from the liver, or "myokines" when they are from skeletal muscle). However, insulin resistance is often observed in subjects without obesity or lipodystrophy, especially in non-obese Asians [14].…”

Section: Introductionmentioning

confidence: 99%

Soluble EGFR, a hepatokine, and adipsin, an adipokine, are biomarkers correlated with distinct aspects of insulin resistance in type 2 diabetes subjects

Kyohara

Shirakawa

Okuyama

et al. 2020

Diabetol Metab Syndr

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Background Insulin resistance can occur in all metabolic organs including the liver, adipose tissue, and skeletal muscles. Circulating soluble epidermal growth factor receptor (soluble EGFR) and adipsin levels are altered in obese diabetic mice and are possibly correlated with insulin resistance in both mice and humans. Here, we investigated the significance of soluble EGFR and adipsin as biomarkers for insulin resistance in Japanese subjects with type 2 diabetes. Methods We measured the soluble EGFR and adipsin levels in sera from 47 non-diabetic subjects and 106 subjects with type 2 diabetes using enzyme-linked immunosorbent assays (ELISAs) and analyzed the correlations between the soluble EGFR or adipsin levels and metabolic parameters in type 2 diabetes subjects. We also measured the gene expression levels of Egfr and Cfd (adipsin) in the liver, adipose tissue, and skeletal muscle in mice with/without obesity or diabetes. Results The soluble EGFR levels were correlated with the fasting blood glucose level (P = 0.010), HOMA-IR (P = 0.035), HbA1c level (P = 0.007), HDL-cholesterol level (P = 0.044), and FIB-4 index (P = 0.017) after adjustments for age, sex, and total cholesterol levels. These factors are known to be related to hepatic insulin resistance. The serum adipsin levels were correlated with BMI (P < 0.001), waist circumference (P < 0.001), fasting serum insulin level (P = 0.001), HOMA-IR (P = 0.009), CPR-index (P = 0.045), and FIB-4 index (P = 0.007) after adjustments for age, sex and eGFR levels. Abdominal adiposity leads to the potentiation of these factors. The expression of Egfr was abundant in the liver, while Cfd was predominantly expressed in adipose tissue in mice. Conclusions Soluble EGFR, a hepatokine, is correlated with insulin resistance in the liver, while adipsin, an adipokine, is associated with adipose insulin resistance. Trial registration: UMIN Clinical Trials Registry (www.umin.ac.jp), UMIN000020474. Registered 8 January 2016.

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Fatty Liver Has Stronger Association With Insulin Resistance Than Visceral Fat Accumulation in Nonobese Japanese Men

Cited by 23 publications

References 31 publications

Clinical and anthropometric characteristics of non‐obese non‐alcoholic fatty liver disease subjects in Japan

Clinical and anthropometric characteristics of non‐obese non‐alcoholic fatty liver disease subjects in Japan

Fatty Liver, and Not Visceral Fat, Is More Associated with Liver Fibrosis and Diabetes in Non-Obese Japanese Individuals: A Cross-Sectional Study

Soluble EGFR, a hepatokine, and adipsin, an adipokine, are biomarkers correlated with distinct aspects of insulin resistance in type 2 diabetes subjects

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