Xian Zhang

Adipose tissue metabolic dysfunction plays a central role in the development of obesity and related metabolic disease. Luteolin is a natural flavonoid with antioxidant, anti-inflammatory, antidiabetic, and antiobesity activities, while it is limited by poor solubility, bioavailability, and stability. This study developed a whey protein isolate (WPI)–Pueraria lobata amylopectin (PLA) composite gel, characterized by a dense 3D network and enhanced mechanical strength. The WPI-PLA gel efficiently encapsulated luteolin in a stable amorphous form and exhibited uniform particle size and excellent colloidal stability. This encapsulation improved the light, storage, and thermal stabilities of luteolin; enhanced its antioxidant activity due to improved dispersion; and enabled its preferential intestinal release. Encapsulated luteolin promoted the expression of thermogenic genes UCP1, Pgc-1α, Prdm16, and Cidea and protein levels of UCP1 and catalase in brown-differentiated C3H10T1/2 cells and inhibited the expression of lipopolysaccharide-induced inflammatory cytokines Il-6, Tnf-α, and Il-1β in RAW264.7 macrophages. In differentiated white 3T3-L1 adipocytes, WPI-LU-PLA restored insulin sensitivity impaired by macrophage-conditioned medium. This reversal was indicated by the enhanced expression of the insulin sensitivity-related genes GLUT4 and Irs1, along with increases in GLUT4 and p-Akt protein levels. In conclusion, the WPI-PLA composite gel enhances the stability, bioaccessibility, and bioactivity of luteolin, suggesting potential for functional foods targeting metabolic dysfunction in adipose tissues.

Interleukin 18 (IL18)-Na-Cl cotransporter (NCC) signaling triggers β cell proliferation, development survival and insulin production in islets. Targeting islet insulin production is a potential strategy for hyperglycemia treatment. Dietary flavonoids possess the substantial anti-hyperglycemia activity. However, whether these flavonoids improve hyperglycemia through directly promoting islet insulin production and the underlying mechanism remains unclear. In this study, islets are isolated from wild-type (WT) and Ncc^-/- mice and treated with dietary flavonoids ex vivo. Among the six dietary flavonoids of chrysin, apigenin, luteolin, quercetin, myricetin and kaempferol, 10 μM luteolin and kaempferol exhibit the highest activities in stimulating insulin production in ex vivo islet. Furthermore, luteolin and kaempferol treatments increase IL18 production and NCC expression, enhance β cell proliferation and survival, protect against streptozocin (STZ)-induced apoptosis and damage in islet. However, the deficiency of NCC eliminate these activities of luteolin and kaempferol. Moreover, STZ-induced hyperglycemic mice are fed a diet supplemented with 0.01% luteolin or kaempferol. In vivo studies have shown that dietary supplementation with luteolin or kaempferol improves glucose tolerance and insulin production, alleviates the apoptosis of islet β cells, and elevates IL18 expression in STZ-induced hyperglycemic mice. In conclusion, dietary luteolin and kaempferol promote islet insulin production, proliferation and survival, protect against STZ-induced islet apoptosis and hyperglycemia through IL18-NCC signaling.

Scope: Serotonin (5‐HT)‐induced visceral adipocyte lipolysis is essential for the development of obesity‐related complications. Diet supplementation of luteolin prevents high‐fat diet (HFD)‐fed mice against obesity and associated fatty liver. However, independent of the body weight loss, whether dietary luteolin can substantially reduce hepatic steatosis remains unclear.Methods and results: In differentiated 3T3‐L1 cells, 5‐HT treatment promotes adipocyte lipolysis, while luteolin significantly inhibits 5‐HT‐induced lipolysis, Ca²⁺‐PKG cascade, and SIRT1/FoxO1/AMPKα signaling through binding to 5‐HT receptor HTR2B. Further, 5‐week‐old mice are fed with an HFD for 16 weeks. At the 6th, 8th, or 10th weeks of HFD feeding, some mice are switched to a luteolin‐containing HFD, respectively. In all HFD‐fed mice, body weight gain and body component are unaffected by dietary luteolin. However, diet supplementation of luteolin at the 6th or 8th, rather than at the 10th weeks, alleviates hepatic steatosis. Meanwhile, dietary luteolin reduces epididymal adipose tissue (EAT) lipolysis, and represses the level of lipolytic enzyme, the expression ofHtr2b, and the activation of PKG and SIRT1/FoxO1/AMPKα signaling in EAT.Conclusions: Diet supplementation of luteolin before the formation of fatty liver protects HFD‐fed mice against ectopic lipid deposition in liver by inhibiting visceral adipocyte lipolysis.

Obesity is characterized by excessive body fat accumulation and is a high-risk factor for metabolic comorbidities, including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. In lean individuals, adipose tissue (AT) is not only an important regulatory organ for energy storage and metabolism, but also an indispensable immune and endocrine organ. The sustained energy imbalance induces adipocyte hypotrophy and hyperplasia as well as AT remodeling, accompanied by chronic low-grade inflammation and adipocytes dysfunction in AT, ultimately leading to systemic insulin resistance and ectopic lipid deposition. Luteolin is a natural flavonoid widely distributed in fruits and vegetables and possesses multifold biological activities, such as antioxidant, anticancer, and anti-inflammatory activities. Diet supplementation of this flavonoid has been reported to inhibit AT lipogenesis and inflammation as well as the ectopic lipid deposition, increase AT thermogenesis and systemic energy expenditure, and finally improve obesity and associated metabolic diseases. The purpose of this review is to reveal the nutritional activities of luteolin in obesity and its complications with emphasis on its action on AT energy metabolism, immunoregulation, and endocrine intervention.

Aims: Blood eosinophil (EOS) counts and EOS cationic protein (ECP) levels associate positively with major cardiovascular disease (CVD) risk factors and prevalence. This study investigates the role of EOS in cardiac hypertrophy.Methods and results: A retrospective cross-section study of 644 consecutive inpatients with hypertension examined the association between blood EOS counts and cardiac hypertrophy. Pressure overload- and β-adrenoreceptor agonist isoproterenol-induced cardiac hypertrophy was produced in EOS-deficient ΔdblGATA mice. This study revealed positive correlations between blood EOS counts and left ventricular (LV) mass and mass index in humans. ΔdblGATA mice showed exacerbated cardiac hypertrophy and dysfunction, with increased LV wall thickness, reduced LV internal diameter, and increased myocardial cell size, death, and fibrosis. Repopulation of EOS from wild-type (WT) mice, but not those from IL4-deficient mice ameliorated cardiac hypertrophy and cardiac dysfunctions. In ΔdblGATA and WT mice, administration of ECP mEar1 improved cardiac hypertrophy and function. Mechanistic studies demonstrated that EOS expression of IL4, IL13, and mEar1 was essential to control mouse cardiomyocyte hypertrophy and death and cardiac fibroblast TGF-β signalling and fibrotic protein synthesis. The use of human cardiac cells yielded the same results. Human ECP, EOS-derived neurotoxin, human EOS, or murine recombinant mEar1 reduced human cardiomyocyte death and hypertrophy and human cardiac fibroblast TGF-β signalling.Conclusion: Although blood EOS counts correlated positively with LV mass or LV mass index in humans, this study established a cardioprotective role for EOS IL4 and cationic proteins in cardiac hypertrophy and tested a therapeutic possibility of ECPs in this human CVD.