scholarly journals The hepatic lipidome and HNF4α and SHBG expression in human liver

2020 ◽  
Vol 9 (10) ◽  
pp. 1009-1018
Author(s):  
Stephen J Winters ◽  
Charles R Scoggins ◽  
Duke Appiah ◽  
Dushan T Ghooray

Low plasma levels of sex hormone-binding globulin (SHBG) are a marker for obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The transcription factor HNF4α is a major determinant of hepatic SHBG expression and thereby serum SHBG levels, and mediates in part the association of low SHBG with hyperinsulinemia and hepatic steatosis. We analyzed the lipidome in human liver specimens from a cohort of patients who underwent hepatic resection as a treatment for cancer, providing insight into hepatic lipids in those without extreme obesity or the clinical diagnosis of NAFLD or non-alcoholic steatohepatitis. Both steatosis and high HOMA-IR were associated with higher levels of saturated and unsaturated FA, other than arachidonic, with the most dramatic rise in 18:1 oleate, consistent with increased stearoyl-CoA desaturase activity. Individuals with low HOMA-IR had low levels of total hepatic fatty acids, while both low and high fatty acid levels characterized the high HOMA-IR group. Both insulin resistance and high levels of hepatic fat were associated with low expression levels of HNF4α and thereby SHBG, but the expression of these genes was also low in the absence of these determinants, implying additional regulatory mechanisms that remain to be determined. The relationship of all FA studied to HNFα and SHBG mRNAs was inverse, and similar to that for total triglyceride concentrations, irrespective of chain length and saturation vs unsaturation.

1998 ◽  
Vol 44 (10) ◽  
pp. 2178-2182 ◽  
Author(s):  
Stephen J Winters ◽  
David E Kelley ◽  
Bret Goodpaster

Abstract Men with low testosterone concentrations are usually hypogonadal. However, because variations in the testosterone transport protein, sex hormone-binding globulin (SHBG), directly influence the total testosterone concentration, confirmation of a low testosterone with a measurement of free testosterone or “bioavailable” testosterone (BAT) is recommended. In the present study, we examined the relationship of SHBG with free testosterone (Coat-A-Count assay, Diagnostic Products) and with BAT in men (n = 29) and women (n = 28) who participated in a study of the metabolic determinants of body composition. As expected, total testosterone was strongly positively correlated with SHBG among men (r = 0.68; P <0.01). Although the BAT was independent of SHBG in men (r = 0.02), SHBG was an important predictor of free testosterone (r = 0. 62; P <0.01). In contrast, in women serum concentrations of total testosterone (r = −0.26; P = 0.17), free testosterone (r = −0.30; P = 0.17), and BAT (r = −0.46; P = 0.013) all tended to be lower with increasing SHBG. Free testosterone was nearly perfectly positively correlated with total testosterone (r = 0.97) in men, among whom free testosterone represented a relatively constant percentage of the total testosterone (0.5–0.65%), and the percentage of free testosterone was unrelated to SHBG. Thus the Coat-A-Count free testosterone concentration in men, like the total testosterone concentration, is determined in part by plasma SHBG. Accordingly, androgen deficiency may be misclassified with this assay in men with low SHBG. Moreover, the previous findings of reduced free testosterone concentrations with hypertension or hyperinsulinemia or as a risk factor for developing type 2 diabetes, conditions in which SHBG is reduced, may have been methodology-related.


2019 ◽  
Vol 16 (4) ◽  
pp. 13-25
Author(s):  
Elena-Daniela Grigorescu ◽  
Mariana Floria ◽  
Cristina Mihaela Lăcătușu ◽  
Bogdan Mircea-Mihai ◽  
Ioana Creţu ◽  
...  

AbstractAim. Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are in a bidirectional relationship. This prospective study focused on associations between parameters common to the pathogenesis of insulin resistance, inflammation and hepatic steatosis in T2DM patients with metabolic imbalance.Methods. We used clinical data, insulin resistance and inflammation indices, and hepatic steatosis markers from 120 patients.Results. The patients (44% men, mean age 58) had a mean body mass index (BMI) of 32 kg/m2 and mean T2DM history of 6 years. With exceptions, significant correlations were found between metabolic, inflammatory and hepatic parameters.Conclusions. In T2DM patients with poor glycemic control, hepatic steatosis correlates significantly with insulin resistance and inflammation. Increased prevalence and poor prognosis of these diseases together justify the need for NAFLD screening of diabetic patients.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1812-P
Author(s):  
MARIA D. HURTADO ◽  
J.D. ADAMS ◽  
MARCELLO C. LAURENTI ◽  
CHIARA DALLA MAN ◽  
CLAUDIO COBELLI ◽  
...  

2011 ◽  
Vol 31 (5) ◽  
pp. 1208-1214 ◽  
Author(s):  
Sander J. Robins ◽  
Asya Lyass ◽  
Justin P. Zachariah ◽  
Joseph M. Massaro ◽  
Ramachandran S. Vasan

Vascular ◽  
2021 ◽  
pp. 170853812110327
Author(s):  
Jingsong Cao ◽  
Xuyu Zu ◽  
Jianghua Liu

Atherosclerosis is the leading cause of acute cardiovascular events, and vascular calcification is an important pathological phenomenon in atherosclerosis. Recently, many studies have shown that immune cells are closely associated with the development of atherosclerosis and calcification, but there are many conflicting viewpoints because of immune system complications, such as the pro-atherosclerotic and atheroprotective effects of regulatory B cells (Bregs), T helper type 2 (Th2) cells and T helper type 17 (Th17) cells. In this review, we summarize the studies on the roles of immune cells, especially lymphocytes and macrophages, in atherosclerotic calcification. Furthermore, we prepared graphs showing the relationship between T cells, B cells and macrophages and atherosclerotic calcification. Finally, we highlight some potential issues that are closely associated with the function of immune cells in atherosclerotic calcification. Based on current research results, this review summarizes the relationship between immune cells and atherosclerotic calcification, and it will be beneficial to understand the relationship of immune cells and atherosclerotic calcification.


2019 ◽  
Vol 34 (1) ◽  
pp. 99-117
Author(s):  
Huh Taewook

This study attempts to analyze to what extent governance and sustainable development (SD) empirically appear compatible in the thirtyfive OECD countries through the fuzzy-set ideal type analysis, and identify which ideal types appear coupled or decoupled, and then reveal which countries belong to the coupled types or to the decoupled types. In short, twenty-two countries (including Sweden (fuzzy score, 0.953), Denmark (0.920), Finland (0.914), Norway (0.911) in Type 1 (G*S, ‘strong G-S coupled countries’); and Turkey (0.906), Greece (0.833), Mexico (0.828) in Type 4 (g*s, ‘lite g-s coupled countries’) are in line with the accepted conventions regarding the compatible relationship between governance and SD. On the other hand, the rest of thirteen countries (including USA (fuzzy score, 0.815), Luxembourg (0.721), Australia (0.660) in Type 2 (G*s, ‘G-s decoupled countries’); and Slovenia (0.728), France (0.644), Czech Rep. (0.625) in Type 3 (g*S, ‘g-S decoupled countries’) may indicate that the relationship of governance and SD is in fact experiencing tensions in the national contexts. These findings are characterized by the substance (of SD) and procedure (of governance) divide. Considering the results, this study focuses on the idea of reflexivity or reflexive capacity.


2018 ◽  
Vol 132 (23) ◽  
pp. 2509-2518 ◽  
Author(s):  
Gargi Mahapatra ◽  
S. Carrie Smith ◽  
Timothy M. Hughes ◽  
Benjamin Wagner ◽  
Joseph A. Maldjian ◽  
...  

Blood-based bioenergetic profiling has promising applications as a minimally invasive biomarker of systemic bioenergetic capacity. In the present study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with long-standing Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes. Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology.


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