Serum Adropin as a Potential Biomarker for Predicting the Development of Type 2 Diabetes Mellitus in Individuals With Metabolic Dysfunction-Associated Fatty Liver Disease

Background: Adropin, a peptide translated from the Energy Homeostasis Associated gene (ENHO), was mainly expressed in the liver and was a regulator in metabolic and energy homeostasis. This study aims to investigate the correlation between adropin and histological characteristics of the liver, and the clinical relevance of adropin in patients with metabolic dysfunction-associated fatty liver disease (MAFLD).Methods: A total of 62 subjects, including 32 healthy controls and 30 MAFLD patients, were enrolled in this case-control study. The MAFLD patients were further divided into two subgroups, including NGT-M group and T2DM-M group. Serum adropin levels, metabolic parameters and intrahepatic lipids, the liver ENHO mRNA expressions and histological characteristics were investigated.Results: MAFLD patients showed significantly lower circulating adropin compared with healthy controls (2.02 ± 2.92 vs. 5.52 ± 0.65 ng/mL, P < 0.0001). Subgroup analysis exhibited dramatically declined serum adropin levels in T2DM-M patients compared with NGT-M group (0.51 ± 0.73 vs. 4.00 ± 3.52 ng/mL, P < 0.001). H&E and Oil Red O staining show exacerbated steatohepatitis in T2DM-M patients in contrast with NGT-M group. Furthermore, serum adropin concentrations were negatively correlated with intrahepatic triglyceride (TG), total cholesterol (TC), and NAFLD activity score (NAS) (TG: r = −0.495; TC: r = −0.392; NAS: r = −0.451; all P < 0.05).Conclusions: MAFLD patients showed significantly lower adropin levels than the healthy controls, especially in T2DM patients. Adropin maybe a potential biomarker for predicting the development of MAFLD, especially in T2DM individuals.

The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

Current research indicates that the next silent epidemic will be linked to chronic liver diseases, specifically non-alcoholic fatty liver disease (NAFLD), which was renamed as metabolic-associated fatty liver disease (MAFLD) in 2020. Globally, MAFLD mortality is on the rise. The etiology of MAFLD is multifactorial and still incompletely understood, but includes the accumulation of intrahepatic lipids, alterations in energy metabolism, insulin resistance, and inflammatory processes. The available MAFLD treatment, therefore, relies on improving the patient’s lifestyle and multidisciplinary pharmacotherapeutic options, whereas the option of surgery is useless without managing the comorbidities of the MAFLD. Nanotechnology is an emerging approach addressing MAFLD, where nanoformulations are suggested to improve the safety and physicochemical properties of conventional drugs/herbal medicines, physical, chemical, and physiological stability, and liver-targeting properties. A wide variety of liver nanosystems were constructed and delivered to the liver, only those that addressed the MAFLD were discussed in this review in terms of the nanocarrier classes, particle size, shape, zeta potential and offered dissolution rate(s), the suitable preparation method(s), excipients (with synergistic effects), and the suitable drug/compound for loading. The advantages and challenges of each nanocarrier and the focus on potential promising perspectives in the production of MAFLD nanomedicine were also highlighted.

Peak Growth Hormone-Releasing Hormone-Arginine-Stimulated Growth Hormone Is Inversely Associated with Intramyocellular and Intrahepatic Lipid Content in Premenopausal Women with Obesity

Context: Visceral adiposity is a strong determinant of GH secretion, and low endogenous GH secretion is associated with increased insulin resistance, a key component of the metabolic syndrome. Increased fat accumulation in skeletal muscle and liver may play an etiological role in the development of insulin resistance and other complications of the metabolic syndrome. Little is known about the role of decreased endogenous GH secretion in the pathogenesis of insulin resistance in obesity. Objective: To investigate the relationship between intramyocellular lipids (IMCL), intrahepatic lipids, and peak-stimulated GH in premenopausal women with obesity. Design and Setting: We conducted a cross-sectional study at a clinical translational research center. Patients: Patients included 21 premenopausal women with obesity (mean body mass index, 34.0 ± 4.5 kg/m2) and 17 normal-weight controls (mean body mass index, 21.9 ± 2.0 kg/m2) of comparable mean age. Main Outcomes Measures: IMCL and intrahepatic lipids were measured with proton magnetic resonance spectroscopy (1H-MRS). Body composition was measured with magnetic resonance imaging. Peak GH was measured after stimulation with GHRH-arginine. Results: Obese subjects had higher IMCL, intrahepatic lipids, abdominal and thigh fat, and thigh muscle mass compared with normal-weight controls. There were strong inverse associations between peak GH and both IMCL and intrahepatic lipids independent of age and visceral adiposity. There were positive associations between IMCL and intrahepatic lipids with measures of insulin resistance and serum triglycerides. Conclusion: In premenopausal women with obesity, peak GH is inversely associated with IMCL and intrahepatic lipids independent of age and visceral adiposity. This suggests that low GH may contribute to insulin resistance in obesity through effects on muscle and intrahepatic lipids. Peak growth hormone after GHRH-arginine stimulation is inversely associated with intramyocellular and intrahepatic lipids in premenopausal women with obesity.