Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Its pathogenesis is complex and not yet fully understood. Over the years many studies have proposed various pathophysiological hypotheses, among which the currently most widely accepted is the “multiple parallel hits” theory. According to this model, lipid accumulation in the hepatocytes and insulin resistance increase the vulnerability of the liver to many factors that act in a coordinated and cooperative manner to promote hepatic injury, inflammation and fibrosis. Among these factors, adipose tissue dysfunction and subsequent chronic low grade inflammation play a crucial role. Recent studies have shown that vitamin D exerts an immune-regulating action on adipose tissue, and the growing wealth of epidemiological data is demonstrating that hypovitaminosis D is associated with both obesity and NAFLD. Furthermore, given the strong association between these conditions, current findings suggest that vitamin D may be involved in the relationship between adipose tissue dysfunction and NAFLD. The purpose of this review is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to adipose tissue dysfunction, and in the pathophysiology linking vitamin D deficiency with NAFLD and adiposity, together with an overview of the evidence available on the clinical utility of vitamin D supplementation in cases of NAFLD.

Association between Vitamin D Status and Non-Alcoholic Fatty Liver Disease: A Population-Based Study

“…Vitamin D also has anti-inflammatory and immune-modulatory activity. A lower vitamin D level results in adipose tissue dysfunction and subsequent chronic inflammation, which may also contribute to the development of NAFLD (20,25,26). Furthermore, ananimal study indicated that vitamin D deficiency is related to the development and progression of NAFLD through the activation of TLR2 and TLR4 via CD14/ LBP, and stimulation of the downstream inflammatory signaling molecules involved with steatosis in the liver (27).…”

Correction of insulin resistance in patients with nonalcoholic fatty liver disease with overweight and obesity

“…Спільним патогенетичним механізмом розвитку ішемічної хвороби серця та неалкогольного стеатогепатиту являється активація процесів перекисного окиснення ліпідів на фоні дії агресивних вільних радикалів, що зумовлюється низькою функціональною активністю системи антиоксидантного захисту [4]. Одним із найбільш значущих чинників у патогенезі НАЖХП є ожиріння, яке посилює розвиток ІР [5]. У ряді досліджень відзначено, що резистентність до інсуліну є характерною особливістю НАЖХП, незалежно від наявності ожиріння [6].…”

The Protective Effect of Cynara Cardunculus Extract in Diet-Induced NAFLD: Involvement of OCTN1 and OCTN2 Transporter Subfamily

“…In particular, evidence has been accumulated that, in NAFLD, mitochondrial functionality is impaired mainly due to the increased mitochondrial oxidation deriving from greater FFA availability [10][11][12][13]. Furthermore, in NAFLD the oxidation of peroxisomes and microsomes occurring at the level of endoplasmic reticulum (ER) is stimulated by a greater availability of hepatic FFA, being the latter re-esterified in triglycerides and assembled in VLDL (very low density lipoproteins) [14][15][16][17][18][19].…”