Explore the vast range of titles available.

This study is to investigate the relationship between berberine (BBR) and mitochondrial complex I in lipid metabolism. BBR reversed high-fat diet-induced obesity, hepatic steatosis, hyperlipidemia and insulin resistance in mice. Fatty acid consumption, β-oxidation and lipogenesis were attenuated in liver after BBR treatment which may be through reduction in SCD1, FABP1, CD36 and CPT1A. BBR promoted fecal lipid excretion, which may result from the reduction in intestinal CD36 and SCD1. Moreover, BBR inhibited mitochondrial complex I-dependent oxygen consumption and ATP synthesis of liver and gut, but no impact on activities of complex II, III and IV. BBR ameliorated mitochondrial swelling, facilitated mitochondrial fusion, and reduced mtDNA and citrate synthase activity. BBR decreased the abundance and diversity of gut microbiome. However, no change in metabolism of recipient mice was observed after fecal microbiota transplantation from BBR treated mice. In primary hepatocytes, BBR and AMPK activator A769662 normalized oleic acid-induced lipid deposition. Although both the agents activated AMPK, BBR decreased oxygen consumption whereas A769662 increased it. Collectively, these findings indicated that BBR repressed complex I in gut and liver and consequently inhibited lipid metabolism which led to alleviation of obesity and fatty liver. This process was independent of intestinal bacteria.

Glucose and lipid metabolism disorders are the core pathological mechanism of a variety of metabolic diseases, and the incidence of related diseases is increasing year by year, which seriously threatens human life and health. Traditional Chinese medicine with medicinal and edible properties refers to Chinese medicinal resources that have both medicinal and edible characteristics. Due to its safety and its health-promoting and medicinal functions, traditional Chinese medicine has received increasing attention in the development of functional health foods. Phenolic acids are important secondary metabolites that are ubiquitous in medicinal and edible homologous plants, and the regulation of glycolipid metabolism is an important activity and plays a key role in many diseases. In this paper, we focus on the alleviation of glycolipid disorders using MEHH phenolic acids, which regulate glucose metabolism and lipid metabolism, improve insulin resistance, inhibit inflammatory responses, alleviate oxidative stress, and regulate intestinal flora; additionally, we summarize the mechanism in order to provide a reference for MEHH phenolic acids in the treatment of glycolipid metabolism diseases.

Osthol (OST), a natural coumarin, exhibits anti-inflammatory and metabolism-regulating potential. This study investigated whether OST ameliorates obesity-associated metabolic dysregulation and inflammation by targeting ADRA1D-mediated T helper 17 (Th17) differentiation. High-fat diet (HFD)-induced obese mice were treated with OST. Metabolic parameters including body/organ weights, serum lipids, hepatic enzymes, and histopathology were assessed. Th17-related and inflammatory markers were evaluated via flow cytometry, ELISA, RT-qPCR, and Western blot. In vitro Th17 differentiation (primary murine CD4⁺ T cells) and lipid metabolism (3T3-L1 adipocytes) models were used. ADRA1D was identified as a key target via bioinformatics and validated through overexpression in cells and mice. OST significantly reduced HFD-induced weight gain, liver and fat mass, serum triglycerides (TG), free fatty acids (FFA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic lipid deposition, and adipocyte hypertrophy. OST suppressed Th17 differentiation, CD4⁺IL-17A⁺ and CD4⁺RORγt⁺ cell proportions, and pro-inflammatory cytokines (IL-17A, IL-6, TNF-α), while elevating anti-inflammatory cytokines (IL-10, TGF-β). OST downregulated IL-17RA, TRAF6, and Act1 expression and inhibited ERK1/2 and PI3K phosphorylation. In vitro studies confirmed the dose-dependent inhibitory effect of OST on Th17 polarization. Mechanistically, OST modulated Th17-related signaling via ADRA1D. ADRA1D overexpression partially reversed OST-mediated suppression of Th17 differentiation, expression of lipogenic genes (FASN, PPARγ), and lipid droplet accumulation. In vivo, ADRA1D overexpression attenuated the beneficial effects of OST on metabolic parameters and tissue inflammation, confirming ADRA1D dependence. OST ameliorates obesity-related metabolic dysregulation and inflammation by inhibiting ADRA1D-mediated Th17 differentiation, highlighting ADRA1D as a key mediator and potential therapeutic target for immunometabolic disorders.

Lipid metabolism disorders are a major cause of several chronic metabolic diseases which seriously affect public health. Salusin-α, a vasoactive peptide, has been shown to attenuate lipid metabolism disorders, although its mechanism of action has not been reported. To investigate the effects and potential mechanisms of Salusin-α on lipid metabolism, Salusin-α was overexpressed or knocked down using lentiviral vectors. Hepatocyte steatosis was induced by free fatty acid (FFA) after lentiviral transfection into HepG2 cells. The degree of lipid accumulation was assessed using Oil Red O staining and by measuring several biochemical indices. Subsequently, bioinformatics was used to analyze the signaling pathways that may have been involved in lipid metabolism disorders. Finally, semi-quantitative PCR and western blotting were used to verify the involvement of the liver kinase B1 (LKB1)/AMPK pathway. Compound C, an inhibitor of AMPK, was used to confirm this mechanism's involvement further. The results showed that Salusin-α significantly attenuated lipid accumulation, inflammation and oxidative stress. In addition, Salusin-α increased the levels of LKB1 and AMPK, which inhibited the expression of sterol regulatory element binding protein-1c, fatty acid synthase and acetyl-CoA carboxylase. The addition of Compound C abrogated the Salusin-α-mediated regulation of AMPK on downstream signaling molecules. In summary, overexpression of Salusin-α activated the LKB1/AMPK pathway, which in turn inhibited lipid accumulation in HepG2 cells. This provides insights into the potential mechanism underlying the mechanism by which Salusin-α ameliorates lipid metabolism disorders while identifying a potential therapeutic target.

Lipid metabolism disorders, which are closely linked to obesity, are significantly modulated by the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), a key regulator of glucocorticoid (GC) activation. This study explored the therapeutic potential of H8, a curcumin analog and selective inhibitor of 11β-HSD1, in mitigating these disorders. Employing an in vitro model of GC-induced differentiation in 3T3-L1 adipocytes and an in vivo C57BL/6 mice model characterized by 11β-HSD1 overexpression, we demonstrated that treatment with H8 effectively reduced GC levels in both serum and cultured cells. Lipid accumulation, evaluated through Oil Red O and hematoxylin and eosin (HE) staining, was significantly diminished by H8 in both cellular and animal models. Mechanistic investigations revealed that H8 modulated lipid metabolism through dual mechanisms: inhibition of 11β-HSD1 and activation of the AMP-activated protein kinase (AMPK) signaling pathway. Immunohistochemical and immunofluorescence analyses corroborated these lipid-modulating effects, while RNA and protein profiling identified significant alterations in markers of lipid synthesis. Further examination of the interplay between 11β-HSD1 and AMPK led us to hypothesize that H8 ameliorates lipid metabolism disorders primarily through its inhibitory effects.

Objectives: This study aims to observe the preventive effect of nicotinamide riboside (NR) on fructose-induced lipid metabolism disorders and explore its mechanism. Methods: Male C57BL/6J mice were fed a 20% fructose solution and given 400 mg/kg NR daily by gavage for 10 weeks. Results: The results indicated that NR supplementation significantly reduced the body weight, liver weight, white adipose tissue (WAT) weight, serum, and hepatic lipid levels. NR upregulated the protein expression levels of sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), PR domain containing 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor-gamma coactiva-tor-1-alpha (PGC-1α), nuclear respiratory factor 1-encoding gene (NRF1), mitochondrial transcription factor A (TFAM), cluster of differentiation 137 (CD137), transmembrane protein 26 (TMEM26), and T-box 1 (TBX1). Moreover, NR enhanced the Actinobacteria and Enterorhabdus abundance. Spearman’s correlation analysis revealed that significant correlations exist between Firmicutes, Bacteroidetes, and Erysipelotrichaceae with browning-related indicators. Conclusions: In conclusion, NR could alleviate lipid metabolic abnormalities induced by fructose through activating SIRT1/AMPK-mediated browning of WAT. The mechanism by which NR improves fructose-induced lipid metabolism disorders may also be associated with the modulation of intestinal flora.

Background: NXT629, a PPAR-alpha antagonist, exerts widespread effects in many diseases; however, its function and relevant mechanism in cholesterol gallstones (CG) remain largely unknown. Methods: Male C57BL/6 J mice were fed a regular diet or lithogenic diet (LD), followed by treatment with intraperitoneal injection of NXT629. H&E staining was performed to analyze hepatic pathological changes, and Oil red O staining was conducted to detect lipid accumulation. Concentrations of total cholesterol (TC), triglyceride (TG), phospholipids (PL), total bile acids (TBA), and cholesterol saturation index (CSI) in both bile and serum were analyzed using commercially available kits. The mRNA expressions of ABCG5/8, CYP7A1, CYP7B1, PPAR-α, and ABCB11 in mouse liver tissues were measured by qRT-PCR assay. Overexpression of glycerol-3-phosphate acyltransferase mitochondrial (GPAM) was constructed to investigate the molecular mechanism of NXT629 in CG. Results: NXT629 could prevent the formation of cholesterol gallstones (CG) and improve lipid metabolic disorders in mice fed a lithogenic diet (LD). Treatment with NXT629 significantly reduced the levels of ABCG5, ABCG8, and ABCB11, while increasing the levels of CYP7A1 and CYP7B1 in the LD group. Additionally, NXT629 treatment downregulated GPAM expression in hepatic tissue from LD-fed mice. Overexpression of GPAM partially counteracted the beneficial effects of NXT629 on CG formation, lipid metabolic disorders, and lipid-related gene expressions. Conclusion: NXT629 can inhibit CG formation, improve lipid metabolism disorders and cholesterol homeostasis by inhibiting GPAM expression, suggesting that NXT629 may serve as a potential therapeutic strategy for cholesterol stones prevention and treatment.

Although risk factors for Alzheimer’s disease (AD) involve obesity and elevated low-density lipoprotein (LDL) cholesterol levels, and Lonicera caerulea has been reported to improve lipid metabolism disorders (LMDs), it remains unknown whether Lonicera caerulea can simultaneously modulate the progression of both AD and LMDs. In this study, an integrative strategy combining network pharmacology, Mendelian randomization (MR), molecular docking, and molecular dynamics simulations was employed to explore potential targets, pathways, and causal relationships. Network pharmacology and molecular docking results revealed that several blood–brain barrier (BBB)-permeable active components of Lonicera caerulea, including Naringenin and Palmatine, may be associated with targets involved in the lipid and atherosclerosis pathway, such as HSP90AA1, SRC and TNF. These associations indicate a potential link between the modulation of lipid metabolism and AD-related processes, although further validation is required. Molecular dynamics simulations were conducted to support the stability of key docking complexes. Given that elevated LDL is a central feature of LMDs and a key indicator of cholesterol imbalance, MR analysis was conducted to assess its causal relationship with AD. The results provided genetic evidence supporting a causal role of elevated LDL in AD risk, reinforcing the epidemiological link between lipid metabolism and neurodegeneration. These findings imply that BBB-permeable constituents of Lonicera caerulea may exert multi-target effects relevant to AD and LMDs. Enrichment analysis further indicates a possible involvement of pathways associated with lipid and atherosclerosis, supporting its potential as a dietary strategy for at-risk populations.

Abstract Context Identification of modifiable risk factors, including genetic and acquired disorders of lipid and lipoprotein metabolism, is increasingly recognized as an opportunity to prevent premature cardiovascular disease (CVD) in at-risk youth. Pediatric endocrinologists are at the forefront of this emerging public health concern and can be instrumental in beginning early interventions to prevent premature CVD-related events during adulthood. Aim In this article, we use informative case presentations to provide practical approaches to the management of pediatric dyslipidemia. Cases We present 3 scenarios that are commonly encountered in clinical practice: isolated elevation of low-density lipoprotein cholesterol (LDL-C), combined dyslipidemia, and severe hypertriglyceridemia. Treatment with statin is indicated when the LDL-C is ≥190 mg/dL (4.9 mmol/L) in children ≥10 years of age. For LDL-C levels between 130 and 189 mg/dL (3.4-4.89 mmol/L) despite dietary and lifestyle changes, the presence of additional risk factors and comorbid conditions would favor statin therapy. In the case of combined dyslipidemia, the primary treatment target is LDL-C ≤130 mg/dL (3.4 mmol/L) and the secondary target non-high-density lipoprotein cholesterol <145 mg/dL (3.7 mmol/L). If the triglyceride is ≥400 mg/dL (4.5 mmol/L), prescription omega-3 fatty acids and fibrates are considered. In the case of triglyceride >1000 mg/dL (11.3 mmol/L), dietary fat restriction remains the cornerstone of therapy, even though the landscape of medications is changing. Conclusion Gene variants, acquired conditions, or both are responsible for dyslipidemia during childhood. Extreme elevations of triglycerides can lead to pancreatitis. Early identification and management of dyslipidemia and cardiovascular risk factors is extremely important.

Abstract Context Severe hypothyroidism has profound effects on lipoprotein metabolism including high-density lipoprotein (HDL) cholesterol elevations but effects on HDL function metrics are unknown. Objective To determine the impact of severe short-term hypothyroidism on HDL particle characteristics, HDL cholesterol efflux capacity (CEC), and HDL antioxidative capacity. Design Observational study with variables measured during severe short-term hypothyroidism (median TSH 81 mU/L) and after 20 weeks of thyroid hormone supplementation (median TSH 0.03 mU/L) (Netherlands Trial Registry ID 7228). Setting University hospital setting in The Netherlands. Patients Seventeen patients who had undergone a total thyroidectomy for differentiated thyroid carcinoma. Main outcome measures HDL particle characteristics (nuclear magnetic resonance spectrometry), CEC (human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma), and HDL anti-oxidative capacity (inhibition of low-density lipoprotein oxidation). Results During hypothyroidism plasma total cholesterol, HDL cholesterol and apolipoprotein A-I were increased (P ≤ 0.001). HDL particle concentration was unchanged, but there was a shift in HDL subclasses toward larger HDL particles (P < 0.001). CEC was decreased (P = 0.035), also when corrected for HDL cholesterol (P < 0.001) or HDL particle concentration (P = 0.011). HDL antioxidative capacity did not change. Conclusion During severe short-term hypothyroidism CEC, an important antiatherogenic metric of HDL function, is impaired. HDL cholesterol and larger HDL particles are increased but HDL particle concentration is unchanged. Combined, these findings suggest that HDL quality and quantity are not improved, reflecting dysfunctional HDL in hypothyroidism.