Serum sex hormone-binding globulin levels are reduced and inversely associated with intrahepatic lipid content and saturated fatty acid fraction in adult patients with glycogen storage disease type 1a.

PURPOSE: De novo lipogenesis has been inversely associated with serum sex hormone-binding globulin (SHBG) levels. However, the directionality of this association has remained uncertain. We, therefore, studied individuals with glycogen storage disease type 1a (GSD1a), who are characterized by a genetic defect in glucose-6-phosphatase resulting in increased rates of de novo lipogenesis, to assess the downstream effect on serum SHBG levels. METHODS: A case-control study comparing serum SHBG levels in patients with GSD1a (n = 10) and controls matched for age, sex, and BMI (n = 10). Intrahepatic lipid content and saturated fatty acid fraction were quantified by proton magnetic resonance spectroscopy. RESULTS: Serum SHBG levels were statistically significantly lower in patients with GSD1a compared to the controls (p = 0.041), while intrahepatic lipid content and intrahepatic saturated fatty acid fraction-a marker of de novo lipogenesis-were significantly higher in patients with GSD1a (p = 0.001 and p = 0.019, respectively). In addition, there was a statistically significant, inverse association of intrahepatic lipid content and saturated fatty acid fraction with serum SHBG levels in patients and controls combined (ß: - 0.28, 95% CI: - 0.47;- 0.09 and ß: - 0.02, 95% CI: - 0.04;- 0.01, respectively). CONCLUSION: Patients with GSD1a, who are characterized by genetically determined higher rates of de novo lipogenesis, have lower serum SHBG levels than controls.

Long-term effects of increased protein intake after weight loss on intrahepatic lipid content and implications for insulin sensitivity: a PREVIEW study.

The aim of this study was to assess the effects of a weight maintenance period comprising two diets differing in protein intake, after weight loss, on intrahepatic lipid content and implications for insulin sensitivity. A total of 25 participants [body mass index (BMI): 31.1 (3.5 kg/m2; intrahepatic lipid (IHL): 8.7 (8.3%; fasting glucose: 6.4 (0.6 mmol/l; homeostatic model assessment for insulin resistance (HOMA-IR): 3.7 (1.6; Matsuda index: 3.4 (2.9] started an 8-wk low-energy diet followed by a 2-yr weight maintenance period with either high protein or medium protein dietary guidelines. At baseline, after 6 mo, and after 2 yr, IHL, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were determined by magnetic resonance spectroscopy/imaging. Glucose and insulin concentrations, determined during an oral glucose challenge, were used to assess the HOMA-IR and Matsuda insulin sensitivity index (ISI). Protein intake was measured with 24-h urinary nitrogen excretion. Protein intake, BMI, IHL, VAT, SAT, HOMA-IR, and ISI did not change differently between the groups during the intervention. In the whole group, BMI, IHL, VAT, SAT, HOMA-IR, and ISI were favorably changed at 6 mo and 2 yr compared with baseline ( P < 0.05). Mixed-model analysis showed that independent of BMI, protein intake (g/d) at 6 mo was inversely related to IHL (coefficient: -0.04; P < 0.05) and VAT (coefficient: -0.01; P < 0.05). Overall, IHL was positively related to HOMA-IR (coefficient: 0.10; P < 0.01) and inversely related to ISI (coefficient: -0.17; P < 0.01), independent of BMI. A 2-yr medium- to high-protein energy-restricted diet reduced IHL and VAT. Independently of changes in BMI, IHL was inversely related to insulin sensitivity.

Quercetin intervention reduced hepatic fat deposition in patients with nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled crossover clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide. However, there is still lack of effective treatment strategies except lifestyle intervention. OBJECTIVES: To evaluate whether quercetin improves intrahepatic lipid content in patients with NAFLD. METHODS: In this randomized, double-blind, placebo-controlled crossover trial, 41 patients with NAFLD were randomly assigned to receive the quercetin (500 mg) or placebo capsules for 12 wk, then switched interventions for another 12 wk after a 4-wk washout period. The primary outcome was intrahepatic lipid content evaluated by magnetic resonance imaging estimated proton density fat fraction. The secondary outcomes were liver function measurements, etc. Safety outcomes included blood routine. RESULTS: A total of 36 patients completed the trial. In intention-to-treat analyses, the quercetin intervention moderately decreased the intrahepatic lipid contents from 11.5% ± 6.4% to 9.6% ± 5.8%, compared with the placebo intervention (decreased by 0.1% ± 2.6%, P = 0.013 and adjusted P value is 0.028). Body weight and body mass index were mildly reduced by 1.5 ± 2.6 kg and 0.5 ± 0.9 kg/m2 after the quercetin intervention (P < 0.05 and both adjusted P values are 0.038), whereas the reductions were only 0.2 ± 1.8 kg and 0.1 ± 0.7 kg/m2 after the placebo intervention. The intrahepatic lipid content reductions were noticeably positively associated with the body weight losses after the quercetin and placebo interventions (r = 0.557 and 0.412, P < 0.001 and P = 0.007, respectively). Subgroup analyses found that the reduction of intrahepatic lipid contents in females (3.0% ± 3.7%) was about twice as large as that in males (1.4% ± 2.5%) with a trend of statistical significance (P = 0.113 and adjusted P value is 0.061). There were no significant differences in other secondary and safety outcomes. No adverse events associated with study intervention were found. CONCLUSIONS: Twelve weeks treatment of quercetin could reduce intrahepatic lipid contents in patients with NAFLD, possibly explained by a slightly larger body weight loss in the quercetin group. TRIAL REGISTRATION: The trial is registered at www.chictr.org.cn as ChiCTR2100047904.

Traditional lifestyle factors partly mediate the association of socioeconomic position with intrahepatic lipid content: The Maastricht study.

Background & Aims: Recent studies have unveiled an association between socioeconomic position (SEP) and intrahepatic lipid (IHL) content. The aim of this study was to examine to what extent traditional lifestyle factors mediate the relationship between SEP and IHL content, independent of aetiology, and non-alcoholic fatty liver disease (NAFLD). Methods: We used cross-sectional data derived from The Maastricht Study (N = 4,001; mean age: 60 years, 49% women, 32% low education level, 21% diabetes, 21% NAFLD). Education, income, and occupation were used as indicators of SEP. Physical activity (accelerometer), intake of total energy, alcohol, saturated fat, protein, vitamin E, dietary fibre, and fructose from sugar-sweetened beverages (SSBs) and fruit juice (food frequency questionnaires) were potential mediators. IHL content was quantified by magnetic resonance imaging. Age, sex, and type 2 diabetes were covariates. Multiple parallel mediation analyses (bootstraps = 10,000) were performed. Results: Individuals with a low education level had a 1.056-fold higher IHL content (95% CI: 1.03-1.08) and a 44% greater NAFLD risk (OR:1.44; 95% CI:1.18-1.77) compared with those with higher education levels. Approximately 8.9% of educational disparity in risk of IHL content was attributable to moderate-to-vigorous physical activity; 6.3% to fructose intake from SSBs; 5.5% to dietary fibre; and -23% to alcohol. Approximately 8.7% of educational disparity in risk of NAFLD was attributable to moderate-to-vigorous physical activity; and 7.7% to fructose intake from SSBs. However, the indirect effect of these mediators was small (0.998 for IHL content and 1.045 for NAFLD) in comparison to the total effect. Similar results were found when income and occupation were used as SEP indicators. Conclusions: Societal measures may alleviate the burden of NAFLD and further studies that identify mediators other than traditional lifestyle factors are warranted to define the relationship underlying SEP and IHL content. Impact and implications: Individuals with a low or medium level of education, income, or occupational status had more fat accumulation in their livers than individuals with a higher education, income, or occupational status. This difference may be attributed to the influence of unhealthy lifestyle factors, such as reduced physical activity and a higher intake of sugar-sweetened beverages among individuals with lower socioeconomic position. Nevertheless, other yet unknown factors may also play a role.

No effect of resveratrol supplementation after 6 months on insulin sensitivity in overweight adults: a randomized trial.

BACKGROUND: Effects of resveratrol on metabolic health have been studied in several short-term human clinical trials, with conflicting results. Next to dose, the duration of the clinical trials may explain the lack of effect in some studies, but long-term studies are still limited. OBJECTIVES: The objective of this study was to investigate the effects of 6-mo resveratrol supplementation on metabolic health outcome parameters. METHODS: Forty-one overweight men and women (BMI: 27-35 kg/m2; aged 40-70 y) completed the study. In this parallel-group, double-blind clinical trial, participants were randomized to receive either 150 mg/d of resveratrol (n = 20) or placebo (n = 21) for 6 mo. The primary outcome of the study was insulin sensitivity, using the Matsuda index. Secondary outcome measures were intrahepatic lipid (IHL) content, body composition, resting energy metabolism, blood pressure, plasma markers, physical performance, quality of life, and quality of sleep. Postintervention differences between the resveratrol and placebo arms were evaluated by ANCOVA adjusting for corresponding preintervention variables. RESULTS: Preintervention, no differences were observed between the 2 treatment arms. Insulin sensitivity was not affected after 6 mo of resveratrol treatment (adjusted mean Matsuda index: 5.18 ± 0.35 in the resveratrol arm compared with 5.50 ± 0.34 in the placebo arm), although there was a significant difference in postintervention glycated hemoglobin (HbA1c) between the arms (P = 0.007). The adjusted means showed that postintervention HbA1c was lower on resveratrol (35.8 ± 0.43 mmol/mol) compared with placebo (37.6 ± 0.44 mmol/mol). No postintervention differences were found in IHL, body composition, blood pressure, energy metabolism, physical performance, or quality of life and sleep between treatment arms. CONCLUSIONS: After 6 mo of resveratrol supplementation, insulin sensitivity was unaffected in the resveratrol arm compared with the placebo arm. Nonetheless, HbA1c was lower in overweight men and women in the resveratrol arm. This trial was registered at Clinicaltrials.gov as NCT02565979.

Liraglutide Reduces Visceral and Intrahepatic Fat Without Significant Loss of Muscle Mass in Obese Patients With Type 2 Diabetes: A Prospective Case Series.

BACKGROUND: Glucagon-like peptide-1 receptor agonists have been reported to reduce body fat as well as improving glycemic control in obese patients with type 2 diabetes. However, the maximum dose of liraglutide is limited to 0.9 mg in Japan, while the international dose is 1.8 mg; and the effect of this low dose on body composition has not been assessed in detail. Accordingly, this study was performed to evaluate the effect of liraglutide on body composition when administered at 0.9 mg once daily for 24 weeks. METHODS: Nine patients were enrolled and started liraglutide at 0.3 mg once daily, which was titrated to 0.9 mg once daily after 1 - 2 weeks and continued for 24 weeks. To comprehensively investigate changes of body composition, the body fat and muscle weight were determined by dual energy absorptiometry, visceral fat volume (VFV) and abdominal subcutaneous fat volume (SFV) were measured by abdominal computed tomography (CT), and the intrahepatic lipid content (IHL) was assessed by proton magnetic resonance spectroscopy. Measurements were obtained before starting liraglutide therapy and after 12 and 24 weeks of treatment. RESULTS: Fasting plasma glucose was significantly reduced from 127 ± 22 to 101 ± 14 mg/dL at 24 weeks and hemoglobin A1c (HbA1c) showed significant reduction from 6.4±0.9% to 5.2±0.5%. Body weight was reduced from 103.4 ± 14.7 to 97.0 ± 12.4 kg (mean reduction: 11.7%) and BMI decreased from 37.4 ± 6.4 to 35.0 ± 5.3 kg/m2 (mean reduction: 5.8%). Furthermore, VFV and IHL decreased from 5,192 ± 1,730 to 4,513 ± 1,299 cm3 (mean reduction: 11.9%) and 32.1±12.6% to 15.2±9.2% (mean reduction: 49.2%), respectively, but SFV did not change. Moreover, the fat index was reduced from 14.8 ± 4.4 to 12.9 ± 3.4 kg/m2 (mean reduction: 10.9%), but the skeletal muscle index did not change. CONCLUSIONS: In obese Japanese drug-naive patients who had type 2 diabetes, treatment with liraglutide (0.9 mg once daily for 24 weeks) reduced body fat, especially visceral fat and intrahepatic fat, while having no significant effect on skeletal muscle.

Ipragliflozin, a sodium glucose co-transporter 2 inhibitor, reduces intrahepatic lipid content and abdominal visceral fat volume in patients with type 2 diabetes.

OBJECTIVE: We recently investigated the effect of ipragliflozin, a sodium glucose co-transporter-2 inhibitor (SGLT-2I), in Japanese patients with type 2 diabetes by a 24-week. SGLT-2Is also have an anti-obesity effect, and reduction of body fat has been demonstrated by indirect methods. However, evaluation of the effect on the total visceral fat volume and intrahepatic lipid content has not been performed. RESEARCH DESIGN AND METHODS: We measured the abdominal subcutaneous fat volume (SFV) and visceral fat volume (VFV) by whole abdominal CT scanning, the intrahepatic lipid (IHL) content by proton magnetic resonance spectroscopy (1H-MRS), and the fat mass index (FI) and appendicular skeletal mass index (ASMI) by dual X-ray absorptiometry (DXA) in 20 patients from our previous study. RESULTS: Administration of ipragliflozin at 50 mg/day for 24 weeks significantly reduced SFV, VFV, and IHL. FI and ASMI were also significantly decreased. Changes of VFV and IHL content at 12 weeks were significantly correlated with the change of HbA1c, but no correlation was observed at 24 weeks. CONCLUSION: These findings demonstrate that ipragliflozin decreases visceral and hepatic fat, with improvement of glycemic control possibly being attributable to these changes at least up to 12 weeks.

Proposed cut-off value of the intrahepatic lipid content for metabolically normal persons assessed by proton magnetic resonance spectroscopy in a Japanese population.

AIMS: To determine the threshold intrahepatic lipid (IHL) content separating metabolically normal from abnormal in a Japanese population based on proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: A total of 305 Japanese subjects aged 20-69years were investigated. The subjects underwent general examination, blood tests, and (1)H-MRS of the liver after an overnight fast. They completed a questionnaire about daily drinking habits and their daily alcohol intake was calculated. RESULTS: The median IHL content was 4.7% in men and 1.7% in women, and it increased along with the number of features of metabolic syndrome (MetS). The optimum IHL cut-off value for separating normal subjects from those with at least one feature of MetS was 6.5% in men (AUC of ROC: 0.727, 95%-CI: 0.649-0.804) and 1.8% in women (0.765, 0.685-0.844). Alcohol intake was not correlated with the IHL content according to multiple logistic regression analysis. CONCLUSION: This study demonstrated a close association of IHL with features of MetS and identified IHL content cut-off values for metabolic normality in Japanese subjects.