Hepatic mediators of lipid metabolism and ketogenesis: focus on fatty liver and diabetes

Background: Diabetes mellitus (DM) is a chronic disorder that it is caused by the absence of insulin secretion due to the inability of the pancreas to produce it (type 1 diabetes; T1DM), or due to defects of insulin signaling in the peripheral tissues, resulting in insulin resistance (type 2 diabetes; T2DM). Commonly, the occurrence of insulin resistance in T2DM patients reflects the high prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) manifestation in these individuals. In fact, approximately 60% T2DM patients are also diagnosed to have NAFLD, and this condition is strongly linked with insulin resistance and obesity. NAFLD is the hepatic manifestation of obesity and metabolic syndrome and includes a spectrum of pathological conditions, which range from simple steatosis (NAFL), nonalcoholic steatohepatitis (NASH), and cirrhosis and hepatocellular carcinoma. NAFLD manifestation is followed by a series of hepatic lipid deregulations and the main abnormalities are increased triglyceride levels, increased hepatic production of VLDL and a reduction of VLDL catabolism. During the progression of NAFLD, the production of ketone bodies progressively reduces while hepatic glucose synthesis and output increases. In fact, most of the fat that enters the liver can be disposed through ketogenesis, preventing the development of NAFLD and hyperglycemia. Objective: This review will focus on the pathophysiological aspect of hepatic lipid metabolism deregulation, ketogenesis and its relevance in progression of NAFLD and T2DM. Conclusion: A better understanding of the molecular mediators involved in lipid synthesis and ketogenesis can lead to new treatments for metabolic disorders in the liver, such as NAFLD.

Homozygous truncating NEK10 mutation, associated with primary ciliary dyskinesia: a case report

Background Primary Ciliary Dyskinesia (PCD) is also known as immotile-cilia syndrome, an autosomal recessive disorder of ciliary function, leading to mucus retention in the respiratory system in childhood. Our knowledge in the pathophysiological aspect of this devastating disorder is increasing with the advancement of genetic and molecular testing. Case presentation Here in, we report two siblings with a classical clinical and radiological presentation of PCD. Using whole exome sequencing we identified a homozygous truncating variant (c.3402 T > A); p.(Tyr1134*) in the NEK10 gene. Western bolt analysis revealed a decrease in the expression of NEK10 protein in the patient cells. Conclusions NEK10 plays a central role in the post-mitotic process of cilia assembly, regulating ciliary length and functions during physiological and pathological status. This study highlights the challenges of identifying disease-causing variants for a highly heterogeneous disorder and reports on the identification of a novel variant in NEK10 which recently associated with PCD.

Lifestyle and Pain in Women With Knee Osteoarthritis

Osteoarthritis (OA) is the main cause of pain and disability in the elderly. The disease leads to chronic musculoskeletal pain, characterized by an abnormal excitability of pain conduction pathways, and lifestyle may interfere in this pathophysiological aspect. Thus, the aim of this study was to compare perceived pain, pressure pain threshold, and lifestyle of adult and elderly women with and without knee OA. A total of 143 women were recruited and divided into 2 groups: OA ( n = 68) and control ( n = 75). Volunteers were evaluated for pressure pain tolerance (algometry in vastus medialis and vastus lateralis muscles), perceived pain (visual analogue scale) and lifestyle (FANTASTIC questionnaire). Patients with OA of the present study presented higher weight ( P = .001) and body mass index ( P < .001) than controls. Results also revealed less tolerance to pressure pain ( P < .001) and higher pain perception ( P < .001) in patients with OA. OA group scored significantly lower in lifestyle questionnaire than controls ( P = .03). Patients with OA in the present study who presented lifestyle scores below median presented significantly higher values of pain perception than the ones above it ( P = .03). In conclusion, patients with OA present more sensitivity to pain, more perceived pain, and worse lifestyle than healthy individuals.