Dietary-Induced Low-Grade Inflammation in the Liver

Abstract

The literature describes a close correlation between metabolic disorders and abnormal immune responses, like low-grade inflammation (LGI), which may be one mechanistic link between obesity and various comorbidities, including non-alcoholic fatty liver disease (NAFLD). In our study, we investigated the influence of dietary composition on obesity-derived LGI in the liver. We used a dietary induced obesity mouse model of C57BL/6J mice fed with high fat diet (HFD, 60% fat, 20% protein, 20% carbohydrates) and two different controls. One was rich in carbohydrates (10% fat, 20% protein, 70% carbohydrates), further referred to as the control diet (CD), and the other one is referred to as the standard diet (SD), with a more balanced macronutrient content (9% fat, 33% protein, 58% carbohydrates). Our results showed a significant increased NAFLD activity score in HFD compared to both controls, but livers of the CD group also differed in their macroscopic appearance from healthy livers. Hepatic fat content showed significantly elevated cholesterol concentrations in the CD group. Histologic analysis of the cellular immune response in the liver showed no difference between HFD and CD and expression analysis of immunologic mediators like interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor alpha also point towards a pro-inflammatory response to CD, comparable to LGI in HFD. Therefore, when studying diet-induced obesity with a focus on inflammatory processes, we encourage researchers to carefully select controls and not use a control diet disproportionally rich in carbohydrates.

Effect of Advanced Glycation End-Products and Excessive Calorie Intake on Diet-Induced Chronic Low-Grade Inflammation Biomarkers in Murine Models

“…No change (→) (mRNA) [37] Liver No change (→) (mRNA) [38] [37] Plasma Control:10 pg/mL Affected: 20 pg/mL (↑) (Protein) [37] Control: 15 pg/mL Affected: 9 pg/mL (↓) (Protein) [39] Pro and antiinflammatory Adipokine Adiponectin Plasma Control: 90 µg/mL Affected: 60 µg/mL (↓) (Protein) [40] Control: 30 µg/mL Affected: 45 µg/mL (↑) (Protein) [41] Control: 8 ng/mL (→) (Protein) [37] Cytokine Interleukin 6 (IL-6)…”

“…No change (→) (mRNA) [38] 8-fold change (↑) (mRNA) [44] Myocardium Control: 21 ng/µg Affected: 28 ng/µg (↑) (Protein)…”

“…Adipose tissue 3-fold change (↑) (mRNA) [37] BAL No change (→) (Protein) [42] Brain Control: 0.2 ng/mg Affected: 0.7 ng/mg (↑) (Protein) [36] Kidney 10-fold change (↑) (mRNA) [43] Liver 3-fold change (↑) (mRNA) [38] No change (→) (mRNA) [37] Control: 0.7 ng/mg Affected: 1 ng/mg (↑) (Protein) [36] Myocardium 2-fold change (↑) (mRNA) [45] Plasma Control: 4 pg/mL Affected: 10 pg/mL (↑) (Protein) [39] No change (→) (Protein) [57] Tumor necrosis factor soluble receptor II (TNF-sRII) [36] Liver Control: 10 pg/mL (→) (Protein) [36] IκB kinase (pIKK) Peritone 4-fold change (↑) (mRNA) [46] Mechanistic target of rapamycin (mTOR) Liver Control: 3 ng/mg Affected: 6 ng/mg (↑) (Protein) [52] Protein kinase B (AKT) Adipose tissue 1.5-fold (↓) (mRNA) [41] No change (→) (Protein) [58] LPS presenting protein Despite the fact that we have not attempted to be exhaustive in this review, significant diversity can be observed among the molecular biomarkers of inflammation listed in Table 1. Cytokines and chemokines are by far the most studied molecules, and IL-6, TNF-α, and MCP-1 figure among the most studied biomarkers in dietary studies with animal models.…”

Targeting Inflammation by Anthocyanins as the Novel Therapeutic Potential for Chronic Diseases: An Update

“…This phenomenon has been termed "inflamm-aging" [1,3]. LGI has also been given the name "metaflammation" (an inflammation of metabolic tissue), which originates from metabolic Molecules 2021, 26, 4380 2 of 17 cells in response to excess nutrients [4]. There is a general lack of sensitive and specific biomarkers of low-grade chronic inflammation that can be used in human trials.…”

“…Current research provides links among the change in inflammatory profile and the risk of a number of chronic conditions, including metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), cancer, cardiovascular, and neurodegenerative disease [ 4 , 8 , 9 , 10 , 11 , 12 ].…”