The present review aims to provide a complete and comprehensive summary of current literature relevant to oxysterols and related diseases. Oxidation of cholesterol leads to the formation of a large number of oxidized products, generally known as oxysterols. They are intermediates in the biosynthesis of bile acids, steroid hormones, and 1,25- dihydroxyvitamin D3. Although oxysterols are considered as metabolic intermediates, there is a growing body of evidence that many of them are bioactive, and their absence or excess may be part of the cause of a disease phenotype. These compounds derive from either enzymatic or non-enzymatic oxidation of cholesterol. This study provides comprehensive information about the structures, formation, and types of oxysterols even when involved in certain disease states, focusing on their effects on metabolism and linkages with these diseases. The role of specific oxysterols as mediators in various disorders, such as degenerative (age-related) and cancer-related disorders, has now become clearer. Oxysterol levels may be employed as suitable markers for the diagnosis of specific diseases or in predicting the incidence rate of diseases, such as diabetes mellitus, Alzheimer’s disease, multiple sclerosis, osteoporosis, lung cancer, breast cancer, and infertility. However, further investigations may be required to confirm these mentioned possibilities.

Objectives: The calcium-sensing receptor (CaSR), the major sensor of extracellular Ca²⁺, is expressed in various tissues, including the gastrointestinal tract. Although the essential ligand of CaSR is calcium, its activity can be regulated by aromatic L-amino acids. The expression of CaSR on enteroendocrine cells suggests that CaSR functions as a physiological amino acid sensor for gut hormone release. Here, we investigated the effects of L-tryptophan (L-Trp) on rat glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin secretion, and the role of CaSR in this mechanism in vivo. Methods: The effects of intraduodenal L-Trp on GLP-1, PYY, and insulin secretion were investigated. A CaSR antagonist, NPS 2143, was administered to determine whether CaSR plays a role in L-Trp-mediated gut hormone release. Male Wistar rats were divided into L-Trp, L-Trp+NPS 2143, and L-Trp+vehicle groups. Blood samples were collected, before and after the intraduodenal infusions, for determining plasma glucose, L-Trp, insulin, GLP-1, and PYY levels. Results: Our study showed a significant increase in plasma GLP-1 and insulin levels, but not plasma PYY and glucose levels, following the acute intraduodenal administration of L-Trp. We demonstrated that CaSR plays a role in L-Trp-mediated GLP-1 secretion due to attenuation of GLP-1 release with the CaSR antagonist NPS 2143. Discussion: We demonstrated that GLP-1, but not PYY, secretion following intraduodenal L-Trp administration was mediated through calcium-sensing receptors. This mechanism underlying protein sensing in the gastrointestinal system may be important for the development of new therapeutic strategies without side effects for obesity and diabetes.

Context Nonalcoholic fatty liver disease (NAFLD) is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been validated to identify high-risk patients. Patients with NAFLD have been shown to have higher serum angiopoietin-like protein-8 (ANGPTL-8) levels. Objective The risk of NAFLD is known insufficiently in acromegaly. Moreover, the utility of the NS and the link between NAFLD and ANGPTL-8 in acromegaly is unknown. Methods Thirty-two patients with acromegaly (n = 15, active [AA] and n = 17, controlled acromegaly [CA]) and 19 healthy controls were included. Magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) was used to evaluate hepatic steatosis, and magnetic resonance elastography to evaluate liver stiffness measurement. ANGPTL-8 levels were measured with ELISA. Results Median liver MRI-PDFF and NAFLD prevalence in AA were lower than in CA (P = .026 and P < .001, respectively). Median magnetic resonance elastography-liver stiffness measurement were similar across groups. Of the NS, visceral adiposity index, fatty liver index, hepatic steatosis index, and triglyceride-glucose index (TyG) all showed positive correlation with the liver MRI-PDFF in the control group. However, only TyG significantly correlated with liver fat in the AA and CA groups. There was no correlation between traditional NAFLD risk factors (body mass index, waist circumference, C-reactive protein, homeostasis model assessment for insulin resistance, visceral adipose tissue) and liver MRI-PDFF in the AA and CA. Patients with acromegaly with NAFLD had lower GH, IGF-1, and ANGPTL-8 levels than in those without NAFLD (P = .025, P = .011, and P = .036, respectively). Conclusion Active acromegaly may protect from NAFLD because of high GH. In patients with acromegaly, NAFLD risk cannot be explained with classical risk factors; hence, additional risk factors must be identified. TyG is the best score to evaluate NAFLD risk. Lower ANGPTL-8 in patients with acromegaly and NAFLD implies this hormone may be raised because of insulin resistance rather than being a cause for NAFLD.