The liver plays a central role in energy metabolism. Dysregulated hepatic lipid metabolism is a major cause of non-alcoholic fatty liver disease (NAFLD), a chronic liver disorder closely linked to obesity and insulin resistance. NAFLD is rapidly emerging as a global health problem with currently no approved therapy. While early stages of NAFLD are often considered benign, the disease can progress to an advanced stage that involves chronic inflammation, with increased risk for developing end-stage disease including fibrosis and liver cancer. Hence, there is an urgent need to identify potential pharmacological targets. Ca²⁺ is an essential signaling molecule involved in a myriad of cellular processes. Intracellular Ca²⁺ is intricately compartmentalized, and the Ca²⁺ flow is tightly controlled by a network of Ca²⁺ transport and buffering proteins. Impaired Ca²⁺ signaling is strongly associated with endoplasmic reticulum stress, mitochondrial dysfunction and autophagic defects, all of which are etiological factors of NAFLD. In this review, we describe the recent advances that underscore the critical role of dysregulated Ca²⁺ homeostasis in lipid metabolic abnormalities and discuss the feasibility of targeting Ca²⁺ signaling as a potential therapeutic approach.

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver diseases worldwide, ranges from simple steatosis to steatohepatitis, with the risk for progressive fibrosis or even cirrhosis. While simple steatosis is a relatively benign condition, the buildup of toxic lipid metabolites can induce chronic inflammation, ultimately triggering disease progression. Pigment epithelium-derived factor (PEDF) is a secreted, multifunctional glycoprotein with lipid metabolic activities. PEDF promotes lipolysis through binding to adipose triglyceride lipase (ATGL), a key enzyme for triglyceride breakdown. In the current study, we aimed to delineate how changes in PEDF expression affect hepatic lipid accumulation. Our data revealed that hepatic PEDF was downregulated in a mouse NAFLD model. We further showed that decreased PEDF levels in hepatocytes in vitro resulted in elevated fatty acid uptake and lipid droplet formation, with concomitant upregulation of fatty acid transport proteins CD36 and fatty acid binding protein 1 (FABP1). RNA sequencing analysis of PEDF knocked down hepatocytes revealed an alteration in gene expression profile toward lipid accumulation. Additionally, decreased PEDF promotes mobilization of fatty acids, an observation distinct from blocking ATGL activity. Taken together, our data suggest that hepatic PEDF downregulation causes molecular changes that favor triglyceride accumulation, which may further lead to NAFLD progression.

Background: Living donor liver transplantation (LDLT) has been developed as one of gold standard treatments for end-stage liver disease. Mental health is a required selection criterion for adult living liver donors and may influence the quality of life after operation. Patients and methods: A total of 1,210 potential living donor candidates for liver transplantation (LT) underwent psychosocial evaluation that included a semi-structured interview, multi-choice self-reported inventory (Beck Depression Inventory-2nd edition [BDI-II], Beck Anxiety Inventory [BAI]), and the family APGAR (Adaptability, Partnership, Growth, Affection, Resolve) index. The test results were compared by family relationships, and subgroups were classified based on the donation type: 1) parents to children, 2) grown children to parents, 3) siblings to siblings, 4) spouses to spouses, and 5) other relatives to other relatives. Results: The BDI-II (P < 0.001) and BAI differed considerably according to the donation type in potential donor candidates. Compared with other subgroups, parents donating to their children suffered the most severe psychological stress before LDLT and exhibited more depressive (P < 0.001) and anxiety symptoms. However, the stress associated with grown children donating to their parents, siblings, and spouses was not significantly higher than it was for other relatives. Furthermore, a significant negative correlation existed between family APGAR scores and the severity of depression and anxiety (P < 0.001) among potential donor candidates. Conclusion: These results indicate the importance of understanding potential donor candidates’ psychological characteristics before LT. Greater anxiety and depression may be exhibited by parent donors due to the distress from fears of death or illness of the recipients, or their guilty feeling for their child. Additionally, family dysfunction also revealed more depression and anxiety. Such donor candidates should be given more extensive pre-donation counseling for minimizing pre-LDLT psychological stress.

Most humans depend on sunlight exposure to satisfy their requirements for vitamin D₃. However, the destruction of the ozone layer in the past few decades has increased the risk of skin aging and wrinkling caused by excessive exposure to ultraviolet (UV) radiation, which may also promote the risk of skin cancer development. The promotion of public health recommendations to avoid sunlight exposure would reduce the risk of skin cancer, but it would also enhance the risk of vitamin D₃ insufficiency/deficiency, which may cause disease development and progression. In addition, the ongoing global COVID-19 pandemic may further reduce sunlight exposure due to stay-at-home policies, resulting in difficulty in active and healthy aging. In this review article, we performed a literature search in PubMed and provided an overview of basic and clinical data regarding the impact of sunlight exposure and vitamin D₃ on public health. We also discuss the potential mechanisms and clinical value of phototherapy with a full-spectrum light (notably blue, red, and near-infrared light) as an alternative to sunlight exposure, which may contribute to combating COVID-19 and promoting active and healthy aging in current aged/superaged societies.

Alcohol-associated liver disease (ALD) is a common indication for liver transplantation (LT). Alcohol relapse after LT is associated with graft loss and worse prognosis. Over the past 20 years, the number and prevalence of living donor liver transplantations (LDLTs) have increased in Taiwan. The aims of this retrospective study are to analyze the incidence and risk factors of alcohol relapse after LT at a single center in Taiwan. A total of 98 patients with ALD who underwent LT from January 2012 to December 2018 were retrospectively evaluated by chart review. Pre-transplant characteristics as well as psychosocial and alcoholic history were used to test the possible associations among the risk factors studied and post-LT alcohol relapse. The incidence of post-LT alcohol relapse was 16.3%. The median duration of alcohol relapse after liver transplantation was 28.1 months (range: 1–89.4 months). The cumulative incidence was 12% and 19% at 1 year and 3 years after LT, respectively. The most powerful risk factors were a pre-LT abstinence period less than 6 months and younger age of starting alcohol. For predicting alcohol relapse, the accuracy rate of abstinence less than 6 months was up to 83.7%. In summary, pre-abstinence period plays a role in predicting post-LT alcohol relapse. Post-LT interventions should be considered specifically for the patients with short abstinence period. Long-term follow-up, patient-centered counseling, and enhancement of healthy lifestyle are suggested to prevent alcohol relapse.