Polysaccharides are known to confer protection against glycolipid metabolism disorders (GMD) by regulating intestinal flora. In this study, a heterogeneous acidic heteropolysaccharide with high molecular weight mainly composed of fructose was isolated from Atractylodes macrocephala Koidz (AMP). Supplementation with AMP was shown to improve diet-induced GMD in a rat model, including decreasing the levels of serum triglycerides, total cholesterol, and glucose, and improving hepatic lipidosis and islet cells morphologies. AMP-treated rats also exhibited modified intestinal flora with enrichments of intestinal Lactobacillus and Rothia species, which was accompanied by increased tryptophan metabolites such as indole-3-propionic acid, indole, tryptamine, and tryptophol. These metabolites promote the expression of intestinal aryl hydrocarbon receptor (AhR) in nuclear fractions. AhR activation increased the expression levels of IL-22 and GLP-1 proteins and mRNA. IL-22 reduced systemic LPS by upregulating the expression of tight junction proteins, antimicrobial peptides, and mucin to ameliorate intestinal barrier function, and activated the hepatic IL-22R/Stat3/Acox1 signaling pathway to improve lipid metabolism. GLP-1 activated the pancreatic GLP-1R/p-CREB signaling pathway to ameliorate β-cell injury and improve insulin resistance. Therefore, the intestinal microbial-tryptophan metabolism-AhR pathway was deduced to be a mechanism by which this polysaccharide improves GMD. 

Atractylodes macrocephala Koidz polysaccharide improves glycolipid metabolism disorders through activation of aryl hydrocarbon receptor by gut flora-produced tryptophan metabolites.

Glycolipid metabolic disorders (GLMDs) are various metabolic disorders resulting from dysregulation in glycolipid levels, consequently leading to an increased risk of obesity, diabetes, liver dysfunction, neuromuscular complications, and cardiorenal vascular diseases (CRVDs). In patients with GLMDs, excess caloric intake and a lack of physical activity may contribute to oxidative stress (OxS) and systemic inflammation. This study aimed to review the connection between GLMD, OxS, metainflammation, and the onset of CRVD. GLMD is due to various metabolic disorders causing dysfunction in the synthesis, breakdown, and absorption of glucose and lipids in the body, resulting in excessive ectopic accumulation of these molecules. This is mainly due to neuroendocrine dysregulation, insulin resistance, OxS, and metainflammation. In GLMD, many inflammatory markers and defense cells play a vital role in related tissues and organs, such as blood vessels, pancreatic islets, the liver, muscle, the kidneys, and adipocytes, promoting inflammatory lesions that affect various interconnected organs through their signaling pathways. Advanced glycation end products, ATP-binding cassette transporter 1, Glucagon-like peptide-1, Toll-like receptor-4, and sphingosine-1-phosphate (S1P) play a crucial role in GLMD since they are related to glucolipid metabolism. The consequences of this is system organ damage and increased morbidity and mortality. 

Glycolipid Metabolic Disorders, Metainflammation, Oxidative Stress, and Cardiovascular Diseases: Unraveling Pathways

Purpose To explore the relationships between serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) levels and glucolipid metabolism disorders (GLMD) in obese children and adolescents. Patients and Methods In this cross-sectional study, 105 obese children and adolescents were selected for the detection of TNF-α, IL-6, hs-CRP, and glycolipid metabolism indicators. All participants were divided into elevated TNF-α group (≥8.1 pg/mL; n=49) and normal TNF-α group (<8.1 pg/mL; n=56), elevated IL-6 group (≥5.9 pg/mL; n=13) and normal IL-6 group (<5.9 pg/mL; n=92), elevated hs-CRP group (≥3.0 mg/L; n=44) and normal hs-CRP group (<3.0 mg/L; n=61), respectively. Results Low-density lipoprotein cholesterol (LDL-C) in the elevated TNF-α group was higher than that in the normal TNF-α group (P=0.010). TNF-α was positively correlated with LDL-C (P=0.005). Fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) in the elevated IL-6 group were higher than those in the normal IL-6 group (all for P <0.05), while high-density lipoprotein cholesterol (HDL-C) in the elevated IL-6 group was lower than that in the normal IL-6 group (P<0.001). IL-6 was positively correlated with FINS, 2-hour postprandial insulin, HOMA-IR and triglyceride (all for P <0.01), while was negatively correlated with HDL-C (P=0.006). Moreover, hs-CRP was positively correlated with FINS and HOMA-IR (all for P <0.05). Conclusion There may be correlations between serum TNF-α, IL-6, hs-CRP levels and GLMD in obese children and adolescents. Attention should be paid to monitoring serum inflammatory factors and preventing their elevation in obese children and adolescents, thus reducing the occurrence of GLMD.

Associations Between Serum TNF-α, IL-6, hs-CRP and GLMD in Obese Children and Adolescents: A Cross-Sectional Study

The associations between hematological parameters and the incidence of prehypertension and hypertension in children and adolescents: a prospective cohort study.

Fatty liver disease, a condition characterized by fatty degeneration of the liver, mainly classified as non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), has become a leading cause of cirrhosis, liver cancer and death. The gut-liver axis is the bidirectional relationship between the gut and its microbiota and its liver. The liver can communicate with the gut through the bile ducts, while the portal vein transports the products of the gut flora to the liver. The intestinal flora and its metabolites directly and indirectly regulate hepatic gene expression, leading to an imbalance in the gut-liver axis and thus contributing to the development of liver disease. Utilizing natural products for the prevention and treatment of various metabolic diseases is a prevalent practice, and it is anticipated to represent the forthcoming trend in the development of drugs for combating NAFLD/ALD. This paper discusses the mechanism of the enterohepatic axis in fatty liver, summarizes the important role of plant metabolites in natural products in fatty liver treatment by regulating the enterohepatic axis, and provides a theoretical basis for the subsequent development of new drugs and clinical research.

The gut-liver axis in fatty liver disease: role played by natural products

Background The increased prevalence of glycolipid metabolism disorders (GLMD) in childhood and adolescents has a well-established association with adult type 2 diabetes and cardiovascular diseases; therefore, determinants of GLMD need to be evaluated during this period. Objectives To explore the prevalence of and risk factors for GLMD from the prenatal period through childhood and adolescence. Methods A bidirectional cohort study which was established in 2014 and followed between March 1 and July 20, 2019, was used to illustrate the impact factors for GLMD. Stratified cluster sampling in urban-rural areas was used to include subjects from four communities in Chongqing. 2808 healthy children aged between 6 and 9 years in 2014 entered the cohort in 2014 and followed in 2019 with a follow-up rate of 70%. 2,136 samples (aged 11.68 ± 0.60 years) were included. Results The prevalence rates of insulin resistance (IR), prediabetes/diabetes, and dyslipidemia were 21.02%, 7.19%, and 21.61%, respectively. Subjects with an urban residence, no pubertal development, dyslipidemia in 2014, higher family income, and higher parental education had significantly elevated fasting insulin (FI) or homeostasis model assessment of insulin resistance (HOMA-IR) levels; subjects with female sex, no pubertal development, dyslipidemia in 2014, obesity, gestational hypertension, maternal weight gain above Institute of Medicine guidelines, and single parents had increased triglyceride or triglyceride/high-density lipoprotein (HDL). Adolescents with rural residence had higher HbA1c level. Conclusion We observed that the prevalence of GLMD was high in childhood and adolescents, and rural-urban areas, sex, pubertal development, dyslipidemia in a younger age, maternal obesity, and hypertension were associated with increased GLMD risk, suggesting that implementing the community-family intervention to improve the GLMD of children is essential.

The Determinants of Adolescent Glycolipid Metabolism Disorder: A Cohort Study

Metabolic associated fatty liver disease is the main cause of chronic liver disease in the world, but there is still no effective treatment. In the search for drugs to treat liver steatosis, we screened 303 natural products using HepG2 cells and discovered that perillartine derived from Perilla frutescens (L.) improved fat deposition as well as glucose homeostasis in hepatocytes. In vitro, perillartine reduced the expression of genes involved in lipid synthesis, lipid transport, and gluconeogenesis in hepatocytes, increased the number of mitochondria, and upregulated the phosphorylation of Akt. In vivo, perillartine reduced body weight gain and the fat rate, improved glucose metabolism and energy balance, and altered the gut microbial composition in mice given a high-fat diet. In addition, RORγ was identified as a possible target of perillartine through pharmacophore screening. Functional studies revealed that the overexpression of RORγ blocked the effects of perillartine, suggesting that it reduced lipid accumulation and regulated glucose metabolism by inhibiting the transcriptional activity of RORγ. Our results provide new information on a natural product inhibitor for RORγ and reveal that perillartine is a new candidate for the treatment of obesity and metabolic associated fatty liver disease.

Perillartine protects against metabolic associated fatty liver in high-fat diet-induced obese mice.

Rhynchophylline relieves nonalcoholic fatty liver disease by activating lipase and increasing energy metabolism.

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The Determinants of Adolescent Glycolipid Metabolism Disorder: A Cohort Study

Perillartine protects against metabolic associated fatty liver in high-fat diet-induced obese mice.

Rhynchophylline relieves nonalcoholic fatty liver disease by activating lipase and increasing energy metabolism.