Relationships between Alanine Aminotransferase(ALT), Visceral Adipose Tissue(AT) and Metabolic Risk Factors in a Middle-Aged Japanese Population

Oka, Rie; Yagi, Kunimasa; Nakanishi, Chiaki; Konno, Tetsuo; Kawashiri, Masa‐aki; Hayashi, Kenshi; Nohara, Atsushi; Inazu, Akihiro; Yamagishi, Masakazu

doi:10.5551/jat.21790

Cited by 4 publications

(6 citation statements)

References 34 publications

(34 reference statements)

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“…Although some previous studies only reported a remarkable association between ALT and hypertension in people with certain demographic characteristics [ 17 , 27 ], we found a similar association in subgroups, including BMI, HBsAg, sociodemographic characteristics (age, gender, and area) and health-related behaviors (alcohol drinking and cigarette smoking). Furthermore, interaction effects were also found between serum ALT levels and some conventional hypertensive risk factors.…”

Section: Discussionsupporting

confidence: 67%

“…Some studies revealed that plasma ALT was related to blood pressures (BP) [ 15 ], and the prevalence of hypertension was obviously increased with serum ALT levels [ 16 ]. Other studies did not reveal a substantial association between serum ALT and hypertension because of small sample size [ 13 , 17 ] or multiple metabolic confounding risk factors in research objects [ 17 ]. Meanwhile, a gender difference was found, the association between ALT and hypertension or BP levels was only discovered among males [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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The association between serum alanine aminotransferase and hypertension: A national based cross-sectional analysis among over 21 million Chinese adults

Jia

Yang

Liu

et al. 2021

BMC Cardiovasc Disord

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Background Inconsistent results were found in the association between serum alanine aminotransferase (ALT) and hypertension among population-based studies. This study evaluated the association between ALT and hypertension among Chinese reproductive-age population by utilizing registration data from National Free Pre-pregnancy Checkups Project in 2016–2017. Methods The 21,103,790 registered participants were eligible for analysis, including women who were 20–49 years old and men who were 20–59 years old with available data for ALT and blood pressure (BP). Logistic regression was conducted to estimate odds ratio (OR) for the association between ALT and hypertension as a binary outcome. Linear regression was used to examine the association between ALT and BP as a continuous outcome. Results In total, 4.21% of the participants were hypertensive, and 11.67% had elevated ALT (> 40 U/L). Hypertension prevalence was 3.63% and 8.56% among participants with normal and elevated ALT levels. A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders. The multivariable-adjusted ORs for hypertension were 1, 1.22 (1.21, 1.22), 1.67 (1.65 1.68), 1.78 (1.76, 1.80), and 1.92 (1.90, 1.94) in participants with ALT levels of ≤ 20, 20.01–40, 40.01–60, 60.01–80, and > 80 U/L, respectively. Systolic and diastolic BPs rose by 1.83 and 1.20 mmHg on average, for each 20 U/L increase in ALT (P for trend < 0.001). The association was consistent among subgroups and tended to be stronger among populations who are overweight (body mass index ≥ 24 kg/m2) (χ2 = 52,228, P < 0.001), alcohol drinking (χ2 = 100,730, P < 0.001) and cigarette smoking (χ2 = 105,347, P < 0.001). Conclusions Our cross-sectional analysis suggested a linear association between serum ALT and hypertension or BP, which indicated that abnormal liver metabolism marked by elevated serum ALT could play a role in hypertension or elevated BP condition.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

The association between serum alanine aminotransferase and hypertension: A national based cross-sectional analysis among over 21 million Chinese adults

Jia

Yang

Liu

et al. 2021

BMC Cardiovasc Disord

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“…The serum E2 levels were similar in the two groups, however, the FSH levels were significantly increased in the peri-menopausal group. Furthermore, we adjusted the data by considering the effects of E2 and other confounders (e.g., age, BMI) using multivariate models 2,41 and ultimately found that the serum FSH levels were independently and positively correlated with the cholesterol levels.…”

Section: Discussionmentioning

confidence: 99%

“…Multivariable linear regression model was used to analyze the association between FSH and cholesterol levels, with adjustment for estradiol levels and previously reported potential confounders. 2,41 Two-tailed P values less than 0.05 were considered statistically significant. The analyses were performed using SPSS version 22.0 for Windows (Chicago, IL, USA).…”

Section: Discussionmentioning

confidence: 99%

Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol

et al. 2018

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Menopause is associated with dyslipidemia and an increased risk of cardio-cerebrovascular disease. The classic view assumes that the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen. In addition to a decrease in estrogen, circulating follicle-stimulating hormone (FSH) levels become elevated at menopause. In this study, we find that blocking FSH reduces serum cholesterol via inhibiting hepatic cholesterol biosynthesis. First, epidemiological results show that the serum FSH levels are positively correlated with the serum total cholesterol levels, even after adjustment by considering the effects of serum estrogen. In addition, the prevalence of hypercholesterolemia is significantly higher in peri-menopausal women than that in premenopausal women. Furthermore, we generated a mouse model of FSH elevation by intraperitoneally injecting exogenous FSH into ovariectomized (OVX) mice, in which a normal level of estrogen (E2) was maintained by exogenous supplementation. Consistently, the results indicate that FSH, independent of estrogen, increases the serum cholesterol level in this mouse model. Moreover, blocking FSH signaling by anti-FSHβ antibody or ablating the FSH receptor (FSHR) gene could effectively prevent hypercholesterolemia induced by FSH injection or high-cholesterol diet feeding. Mechanistically, FSH, via binding to hepatic FSHRs, activates the Gi2α/β-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter, thus preventing FoxO1 from repressing SREBP-2 gene transcription. This effect, in turn, results in the upregulation of SREBP-2, which drives HMGCR nascent transcription and de novo cholesterol biosynthesis, leading to the increase of cholesterol accumulation. This study uncovers that blocking FSH signaling might be a new strategy for treating hypercholesterolemia during menopause, particularly for women in peri-menopause characterized by FSH elevation only.

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“…ALT and AST are two key biomarkers of hepatic injury. An increased ALT/AST level is considered to reflect liver fat aggregation when alcohol consumption and viral hepatitis are excluded from the causes of fatty liver . These results indicated that the 5 week BBR‐CS/PT‐NPs treatment could successfully protect the HFD‐fed hamsters from hepatic steatosis and injury.…”

Section: Resultsmentioning

confidence: 91%

Dual‐Stimuli‐Responsive Gut Microbiota‐Targeting Berberine‐CS/PT‐NPs Improved Metabolic Status in Obese Hamsters

Guo

Zheng

et al. 2019

Adv Funct Materials

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Gut dysbiosis has been found to be involved in the pathogenesis of energy metabolic disorders and might be a new strategy for these ailments. Berberine (BBR), a botanical medicine, shows therapeutic efficacy in patients with metabolic diseases. Numerous reports have shown BBR's modulating effect on gut microbiota, opening a new avenue to understand BBR's mechanism. In this study, a colon‐specific delivery system, BBR‐CS/PT‐NP, is investigated by the assembly of pH/gut microflora dual stimuli‐responsive nanoparticles for enhancing the interaction between BBR and gut microbiota. After oral administration, the delivering system remains stable in the stomach and small intestine, followed by a burst release of BBR after reaching the colon segment rich in intestinal bacteria. The enzymes produced by bacteria degrade the nanoparticle, causing direct exposure of BBR to gut microbiota. In the high fat diet‐induced obese hamsters, BBR‐CS/PT‐NP intervention inhibits weight‐gain and fat deposition, decreases plasma lipids and glucose levels, improves inflammation condition and insulin resistance, alleviates hepatic steatosis, at a level significantly higher than the pure BBR does. The mechanisms might be attributable to the enhanced interaction between BBR and the gut flora. The results provide a novel proof‐of‐concept for drug delivery targeting gut microbiota to ameliorate metabolic disorders.

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Relationships between Alanine Aminotransferase(ALT), Visceral Adipose Tissue(AT) and Metabolic Risk Factors in a Middle-Aged Japanese Population

Cited by 4 publications

References 34 publications

The association between serum alanine aminotransferase and hypertension: A national based cross-sectional analysis among over 21 million Chinese adults

The association between serum alanine aminotransferase and hypertension: A national based cross-sectional analysis among over 21 million Chinese adults

Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol

Dual‐Stimuli‐Responsive Gut Microbiota‐Targeting Berberine‐CS/PT‐NPs Improved Metabolic Status in Obese Hamsters

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