Applied nutritional investigationSerum concentration of fatty acids in children with obesity and nonalcoholic fatty liver disease
Introduction
The increasing prevalence of childhood overweight and obesity, often described as a global pandemic, has emerged as a significant, worldwide problem. Globally, an estimated 5.6% of girls and 7.8% of boys ages 5 to 19 y were obese in 2016 [1,2]. The obesity rate for Polish children and adolescents ages 7 to 18 y is reported to be >14% in girls and >18% in boys [3]. Rising rates of childhood obesity is accompanied by an increased prevalence of other components of metabolic syndrome (MetS) in children such as type 2 diabetes, hypertension, and dyslipidemia [4], [5], [6]. Another obesity-related problem is an increasing incidence of pediatric nonalcoholic fatty liver disease (NAFLD). Currently, it is considered to be the most common liver pathology worldwide, with a prevalence between 3% and 10% [7], [8], [9], [10]. It is suggested that both the presence and the severity of NAFLD may further affect the development of metabolic comorbidities [11,12]. NAFLD can be defined as a chronic liver disease resulting from excessive fat accumulation in the liver. Recently, a lot of attention has been brought to lipotoxicity in the pathogenesis of NAFLD. This term tends to be used to refer to lipid-induced oxidative stress, inflammation, and cell death. It is suggested that it is not only the amount of lipids accumulated in the liver that affects the severity of liver injury but also the type of lipids involved and their mutual interactions. Circulating fatty acids (FAs) represent the major source of hepatic fat accumulation in patients with NAFLD and are among the most commonly discussed molecules involved in lipotoxicity. Serum FA levels depend on a diet, adipose tissue lipolysis, or hepatic de novo lipogenesis. In the insulin-resistant state, which is strongly linked to NAFLD, plasma FA levels are increased despite high insulin levels due to impaired antilipolytic action of this hormone. Moreover, insulin resistance (IR) increases hepatic de novo lipogenesis, which along with the increased absorption of plasma FA, leads to their accumulation in the form of triacylglycerols (TGs) in intracytoplasmic lipid droplets. The excess of FAs that are not esterified and stored as ceramide, diacylglycerols, are lipotoxic to hepatocytes. FAs, either alone or together with other lipid fractions, lead to mitochondrial dysfunction with oxidative stress and generation of reactive oxygen species and endoplasmic reticulum stress with activation of unfolded protein response, which promote hepatic inflammation [13], [14], [15]. Thus, although TGs are the main lipids accumulated in hepatic steatosis, it is suggested that their increased synthesis may play a protective role against FA-mediated lipotoxicity [16,17]. Additionally, hepatic FAs are the main substrate for very low-density lipoproteins (VLDLs) exported to the systemic circulation. Increased export of VLDL leads to increased levels of low-density lipoproteins (LDLs) and TG in plasma and decreased levels of high-density lipoproteins (HDLs), which is linked to an increased risk for atherosclerosis [18]. A large and growing body of literature has investigated the role of FAs in MetS depending on the length of a chain and their saturation. High intake of saturated fatty acids (SFAs) is linked to increased risk for cardiovascular disease [19]. Some in vitro experiments demonstrated that overexposure to SFA promotes lipotoxicity, apoptosis, and liver injury [20]. On the other hand, high intake of monounsaturated fatty acids (MUFAs) were found to ameliorate blood lipid profile, increase lipid oxidation, and decrease IR, which may suggest their potential protective role against NAFLD [21]. On the contrary, polyunsaturated fatty acids (PUFAs) may play a different role depending on theirs saturation. ω-3 PUFAs are considered to have a beneficial, anti-inflammatory effect and protect against liver cell injury, whereas ω-6 PUFA are thought to be associated with proinflammatory actions [22]. Another important aspect is the ω-6/ω-3 PUFA ratio. It is suggested that increased ω-6/ω-3 PUFA ratio is strongly linked to the development of obesity [23]. That is why the potential role of supplementation of ω-3 PUFA in treatment of NAFLD is an object of debate [24]. A considerable amount of literature has been published on FAs in the pathogenesis of various diseases. However, our knowledge on their role in NAFLD is based mostly on adult studies as data on FAs in pediatric NAFLD is very limited. Therefore, the main aim of the present study was to evaluate serum FA concentrations and their saturation status together with complementary correlation with the steatosis degree, anthropometric measurements, metabolic disturbances, and other biochemical parameters in children with obesity and NAFLD.
Section snippets
Methods
This prospective study involved 80 children (60 boys and 20 girls) between 7 and 17 y of age (median, 12 y) whose body mass index (BMI) exceeded the 95th percentile for sex and age. The children were admitted to our department due to suspected liver disease (an elevated serum alanine aminotransferase [ALT] activity and/or ultrasonographic liver brightness and/or hepatology). By the exclusion criteria, patients with viral hepatitis (HCV, HBV, cytomegalovirus), autoimmune hepatitis, toxic
Results
The total number of children with obesity included in the study group was 80 and the predominance of boys was observed (60 boys versus 20 girls). The reference group consisted of 15 children with normal BMI without any somatic organ pathology. Median BMI of the study group was 27.79 kg/m2 (25.85–31.85 kg/m2). As many as 38.75% of all patients with obesity were diagnosed with NAFLD (31 patients). Based on the ultrasonographic imaging, 31 children (38.75%) were identified with advanced steatosis.
Discussion
The aim of this study focused on a detailed concentration of serum FAs (total and selected FAs) in pediatric patients with obesity in relation to their clinical and laboratory data. In the current research, total FA concentration as well as selected FAs (myristic, palmitic, palmitoleic, stearic, oleic, linoleic, arachidic, behenic, lignoceric, and nervonic) concentrations were significantly higher in both children with obesity and those with obesity and NAFLD when compared with the reference
Conclusions
The present study was designed to determine the concentration of FAs in the serum of children and adolescents with obesity and NAFLD. Elevated FA concentrations changed the percentage of certain subgroups of FAs in children with obesity, together with the significant correlation of FAs to lipid profile and IR parameters may suggest their role in the complex pathogenesis of NAFLD. Considerably more work is needed to determine the exact role of FAs in development and progression of this disease,
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2023, NutritionCitation Excerpt :Our results supported these studies and strengthened the causal potential of the association between AA levels and NAFLD. However, there were other studies with contradictory findings or an absence of an association between AA and NAFLD [9,31]. One prospective study involving 80 obese children found no association between circulating AA levels and NAFLD [9].
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This study was funded by Medical University of Bialystok, projects SUB/1/DN/20/002/1143, N/ST/ZB/18/001/1143.