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. 2023 Dec 6;24(24):17174.
doi: 10.3390/ijms242417174.

Reduced Lipopolysaccharide-Binding Protein (LBP) Levels Are Associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and Adipose Inflammation in Human Obesity

Ilaria Barchetta  1 , Flavia Agata Cimini  1 , Federica Sentinelli  2 , Caterina Chiappetta  3 , Claudio Di Cristofano  3 , Gianfranco Silecchia  4 , Frida Leonetti  3 , Marco Giorgio Baroni  5   6 , Maria Gisella Cavallo  1
Affiliations

Reduced Lipopolysaccharide-Binding Protein (LBP) Levels Are Associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and Adipose Inflammation in Human Obesity

Ilaria Barchetta et al. Int J Mol Sci. .

Abstract

Lipopolysaccharide (LPS) and its binding protein LBP have emerged as potential contributors to the progression from overweight/obesity to overt metabolic diseases and NAFLD. While LPS is known to activate hepatocyte inflammation, thus contributing toward NAFLD development, the role of LBP is more intricate, and recent data have shown that experimental reduction in hepatic LBP promotes NAFLD progression. In this cross-sectional investigation, we evaluated circulating LBP in relation to obesity, NAFLD, visceral adipose tissue (VAT) inflammation, and type 2 diabetes (T2D). We recruited 186 individuals (M/F: 81/105; age: 47 ± 10.4 years; BMI: 35.5 ± 8.6 kg/m2); a subgroup (n = 81) underwent bariatric surgery with intra-operative VAT and liver biopsies. LBP levels were higher in obese individuals than non-obese individuals but were inversely correlated with the parameters of glucose metabolism. Reduced LBP predicted T2D independent of age, sex, and BMI (p < 0.001). LBP levels decreased across more severe stages of hepatosteatosis and lobular inflammation, and were inversely associated with VAT inflammation signatures. In conclusion, LBP levels are increased in obese individuals and are associated with a more favorable metabolic profile and lower NAFLD/NASH prevalence. A possible explanation for these findings is that hepatic LBP production may be triggered by chronic caloric excess and facilitate LPS degradation in the liver, thus protecting these individuals from the metabolic consequences of obesity.

Keywords: MAFLD; MASLD; NASH; insulin resistance; liver fibrosis; low-grade inflammation; metabolic syndrome; type 2 diabetes; visceral obesity.

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Conflict of interest statement

The authors declare no conflict of interest. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Images showing liver histology of two representative study participants with (A) non-alcoholic fatty liver disease (NAFLD) or (B) normal liver. Patient (A): NAFLD (NAS) activity score: 4, staging: 0; SAF score: steatosis: 3, ballooning: 0, lobular inflammation: 0. Patient (B): normal liver tissue. Images viewed under ×200 magnification; hematoxylin and eosin staining.
Figure 2
Figure 2
Serum LBP concentration in relation to NAS score for lobular inflammation in liver biopsy. * Spearman’s coefficient. Abbreviations: LBP: lipopolysaccharide-binding protein; NAS: NASH activity score.
Figure 3
Figure 3
Number of CD68+ cells infiltrating the VAT in relation to serum LBP subgroup. Mean ± standard error. Mann–Whitney test was calculated. Abbreviations: LBP: lipopolysaccharide-binding protein; VAT: visceral adipose tissue.
Figure 4
Figure 4
Potential mechanisms associating lower lipopolysaccharide-binding protein (LBP) levels with dysmetabolic conditions in obesity. In obesity, bacterial overgrowth and LPS release into the portal vein trigger systemic inflammation and stimulate pro-inflammatory responses in the liver, resulting in an increased risk of metabolic diseases and NAFLD. LBP may improve hepatic LPS clearance and hide LPS from recognition by TLR4+ macrophages, thus protecting individuals from obesity-associated metabolic disturbances. Dotted arrows show potential metabolic pathways linking LBP levels to metabolic disease in obesity. Abbreviations: NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; LPS: lipopolysaccharide; LBP: LPS-binding protein; HbA1c: glycosylated hemoglobin; FBG: fasting blood glucose.
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