Differential Expression of Lipid Metabolism Genes, CROT and ABCG1, in Obese Patients with Comorbid Depressive Disorder and Risk of MASLD

Abstract

Background: There is accumulating evidence supporting a bidirectional relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and depressive disorder (DD), with possible genetic factors related to hepatic lipid metabolism. Our aim was to analyse the prevalence of DD in patients with obesity at risk of MASLD, and to evaluate the hepatic expression of genes involved in lipid metabolism, in patients with DD.

Methods: In 152 patients with morbid obesity who underwent bariatric surgery, medical data, blood and liver samples were collected. Liver biopsies were scored for MASLD staging were used for gene expression analysis.

Results: The DD prevalence in this cohort was 29.6%, and patients with DD had a significantly higher hepatic expression of the CROT and ABCG1 genes. Moreover, patients in the MASLD group showed significantly higher relative hepatic expression of SREBP1 and ABCG1 genes compared to the normal liver group. Some anthropometric and clinical measures (BMI and DBP) were positively correlated with the expression of SREBP2, ABCG1 and CROT genes, while the expression of CPT1α was negatively correlated with age, SBP and DBP. There was a positive relationship between GGT and ALP levels and the relative expression of ABCG1 and ACC1 genes.

Conclusions: In this study, individuals with morbid obesity demonstrated an elevated prevalence of DD. Moreover, hepatic genetic dysregulation of lipid metabolism may influence the interplay between MASLD and DD in patients with morbid obesity.

Keywords: depression; genetic dysregulation; lipid metabolism; metabolic dysfunction-associated steatotic liver disease; obesity.

Figure 1

Boxplots presenting the hepatic levels of relative expression of (a) SREBP2, (b) ABCA1, (c) ABCG1, (d) CPT1α, (e) CROT, (f) SREBP1, and (g) ACC in CN and DD groups. Each boxplot displays the median and interquartile range (IQR). The x marks indicate outliers, which were identified using the IQR method. SREBP, Sterol Regulatory Element-Binding Protein; ABCA1, ATP-Binding Cassette Transporter A1; ABCG1, ATP-Binding Cassette Subfamily G Member 1; CROT, Carnitine O-Octanoyltransferase; CPT1α, Carnitine Palmitoyltransferase 1α; ACC, Acetyl-CoA Carboxylase; DD, Depression Disorder Group; CN, control group. A.U, arbitrary units. Mann–Whitney test was used to calculate the difference between groups. Significant p values are annotated (p < 0.05).

Figure 2

Boxplots presenting the hepatic levels of relative expression of (a) SREBP2, (b) ABCA1, (c) ABCG1, (d) CPT1α, (e) CROT, (f) SREBP1, and (g) ACC in NL and MASLD groups. Each boxplot displays the median and interquartile range (IQR). The x marks indicate outliers, which were identified using the IQR method. SREBP, Sterol Regulatory Element-Binding Protein; ABCA1, ATP-Binding Cassette Transporter A1; ABCG1, ATP-Binding Cassette Subfamily G Member 1; CROT, Carnitine O-Octanoyltransferase; CPT1α, Carnitine Palmitoyltransferase 1α; ACC, Acetyl-CoA Carboxylase; NL, Normal Liver; MASLD, metabolic dysfunction-associated steatotic liver disease. A.U, arbitrary units. Mann–Whitney test was used to calculate the difference between groups. Significant p values are annotated (p < 0.05).

Figure 3

Heat-map presenting the relationship between the expressions of hepatic genes involved in lipid metabolism and the anthropometric measures, hepatic and immune-metabolic indicators measured in the total cohort. SREBP, Sterol Regulatory Element-Binding Protein; ABCA1, ATP-Binding Cassette Transporter A1; ABCG1, ATP-Binding Cassette Subfamily G Member 1; CROT, Carnitine O-Octanoyltransferase; CPT1α, Carnitine Palmitoyltransferase 1α; ACC, Acetyl-CoA Carboxylase; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HOMA1-IR, homeostatic model assessment method–insulin resistance; HbA1c, glycosylated hemoglobin; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyltransferase; ALP, alkaline phosphatase; CRP, C-reactive protein. Only significant Spearman’s ρ are displayed. p < 0.05 were considered significant.