Anti-Obesity Effect of Jeju Roasted Citrus Peel Extract in High-Fat Diet-Induced Obese Mice and 3T3-L1 Adipocytes Via Lipid Metabolism Regulation.

Lipid accumulation in adipocytes occurs through multifactorial effects such as overnutrition due to unbalanced eating habits, reduced physical activity, and genetic factors. In addition, obesity can be intensified by the dis-regulation of various metabolic systems such as differentiation, lipogenesis, lipolysis, and energy metabolism of adipocytes. In this study, the Jeju roasted peel extract from Citrus unshiu S.Markov. (JRC), which is discarded as opposed to the pulp of C. unshiu S.Markov., is commonly consumed to ameliorate obesity. To investigate the anti-obesity effect of JRC, these studies were conducted on differentiated 3T3-L1 cells and in high-fat diet-induced mice, and related methods were used to confirm whether it decreased lipid accumulation in adipocytes. The mechanism of inhibiting obesity by JRC was confirmed through mRNA expression studies. JRC suppressed lipid accumulation in adipocytes and adipose tissue, and significantly improved enzymes such as alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase and serum lipid profiles. In addition, it effectively modulated the expression of genes related to lipid and energy metabolism in adipose tissue. As a result, these findings suggest that JRC could be a therapeutic regulator of body fat accumulation by significantly alleviating the dis-regulation of intracellular lipid metabolism in adipocytes and by enhancement of energy metabolism (Approval No. CNU IACUC-YB-2023-98).

Comparative Morphology of Island and Inland Agastache rugosa and Their Gastroprotective Effects in EtOH/HCl-Induced Gastric Mucosal Gastritis.

Agastache rugosa Kuntze (Lamiaceae; Labiatae), a medicinal and functional herb used to treat gastrointestinal diseases, grows well both on islands and inland areas in South Korea. Thus, we aimed to reveal the morphological and micromorphological differences between A. rugosa grown on island and inland areas and their pharmacological effects on gastritis in an animal model by combining morphological and mass spectrophotometric analyses. Morphological analysis showed that island A. rugosa had slightly smaller plants and leaves than inland plants; however, the density of all types of trichomes on the leaves, petioles, and stems of island A. rugosa was significantly higher than that of inland plants. The essential oil component analysis revealed that pulegone levels were substantially higher in island A. rugosa than in inland A. rugosa. Despite the differences between island and inland A. rugosa, treatment with both island and inland A. rugosa reduced gastric damages by more than 40% compared to the gastritis induction group. In addition, expression of inflammatory protein was reduced by about 30% by treatment of island and inland A. rugosa. The present study demonstrates quantitative differences in morphology and volatile components between island and inland plants; significant differences were not observed between the gastritis-inhibitory effects of island and inland A. rugosa, and the efficacy of island A. rugosa was found to be similar to that of A. rugosa grown in inland areas.

Citrus Peel Extract Ameliorates High-Fat Diet-Induced NAFLD via Activation of AMPK Signaling.

Non-alcoholic fatty liver disease (NAFLD) is prevalent in the elderly population, and has symptoms ranging from liver steatosis to advanced fibrosis. Citrus peel extracts (CPEs) contain compounds that potentially improve dyslipidemia; however, the mechanism of action and effects on hepatic steatosis regulation remains unclear. Current study was aimed to investigate the protective effect of CPEs extracted through hot-air drying (CPEW) and freeze-drying (CPEF) and the underlying mechanism in a rat model of high-fat diet-induced NAFLD. The high-fat diet (HFD)-fed rats showed significant increase in total cholesterol, alanine aminotransferase (ALT), triglycerides, aspartate aminotransferase (AST), and lipid peroxidation compared to the normal chow-diet (NCD) group rats; but CPEW and CPEF limited this effect. CPEW and CPEF supplementation reduced both hepatocyte steatosis and fat accumulation involving the regulatory effect of mTORC1. Collectively, CPEW and CPEF protected deterioration of liver steatosis with AMPK activation and regulating ROS accumulation associated with interstitial disorders, which are also associated with endoplasmic reticulum (ER) redox. Thus, the application of CPEW and CPEF may lead to the development of novel therapeutic or preventive agents against NAFLD.

Transient Anosmia Induces Depressive-like and Anxiolytic-like Behavior and Reduces Amygdalar Corticotropin-Releasing Hormone in a ZnSO4-Induced Mouse Model.

Olfactory loss is known to affect both mood and quality of life. Transient anosmia was induced in mice to study the resulting changes in mood, behavior, and on a molecular level. Transient anosmia was induced by a single intranasal instillation of ZnSO4 in BALB/c mice. Hematoxylin and eosin (HE) staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression-related behavior; while the open field, and elevated plus maze tests were used to evaluate anxiety-related behavior. The mRNA levels of amygdalar corticotropin-releasing hormone (CRH) and hypothalamic glucocorticoid receptor (GR) were quantified using real-time PCR to confirm relevant molecular change. Olfactory loss was confirmed 1-2.5 weeks after induction, and this loss was subsequently reversed over time. The results of the behavioral tests indicated increased depression-like and reduced anxiety-like behavior at week 1. Accordingly, PCR data identified decreased amygdalar CRH expression at week 1. These results suggest that transient anosmia induces both depressive and anxiolytic behavior as a result of decreased amygdalar CRH in a mouse model of anosmia.

Sasa quelpaertensis and p-coumaric acid attenuate oleic acid-induced lipid accumulation in HepG2 cells.

In this study, we examined the effects of Jeju dwarf bamboo (Sasa quelpaertensis Nakai) extract (JBE) and p-coumaric acid (CA) on oleic acid (OA)-induced lipid accumulation in HepG2 cells. JBE and CA increased the phosphorylation of AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC) and the expression of carnitine palmitoyl transferase 1a (CPT1a) in OA-treated HepG2 cells. Additionally, these compounds decreased sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and OA-induced lipid accumulation, suggesting that JBE and CA modulate lipid metabolism in HepG2 cells via the AMPK activation pathway.

Sasa quelpaertensis Nakai extract and its constituent p-coumaric acid inhibit adipogenesis in 3T3-L1 cells through activation of the AMPK pathway.

In this study, we investigated the effects of Sasa quelpaertensis Nakai extract (SQE) and its main constituent, p-coumaric acid, on adipogenesis in 3T3-L1 cells. SQE markedly inhibited adipogenesis by downregulating the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP-1c), and aP2. It also decreased the expression of fatty acid synthase (FAS) and adiponectin mRNAs in differentiating adipocytes. SQE increased AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation during the early phase of MDI-induced differentiation, suggesting that SQE exerted its anti-adipogenic effect via AMPK activation at an early stage of the differentiation process. p-Coumaric acid suppressed adipogenesis by attenuating the expression of C/EBPα, PPARγ, and SREBP-1c during the late phase of MDI-induced differentiation. In addition, p-coumaric acid increased the phosphorylation of AMPK and ACC, and the expression of carnitine palmitoyl transferase-1 (CPT-1) mRNA, in fully differentiated adipocytes, indicating that it promotes fatty acid ß-oxidation via AMPK signaling. Taken together, our data suggest that SQE and p-coumaric acid might have the anti-obesitic effects via AMPK pathway in 3T3-L1 cells.

Effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes.

Sinensetin is a rare polymethoxylated flavone found in certain citrus fruits. In this study, we investigated the effects of sinensetin on lipid metabolism in mature 3T3-L1 adipocytes. Sinensetin decreased the expression of sterol regulatory element-binding protein 1c (SREBP1c), suggesting its antiadipogeneic property via downreguation of SREBP1c. Also, sinensetin increased the phosphorylation of protein kinase A and hormone-sensitive lipase, indicating its lipolytic property via a cAMP-mediated signaling pathway. Moreover, sinensetin inhibited insulin-stimulated glucose uptake by decreasing the phosphorylation of insulin receptor substrate and Akt. Furthermore, sinensetin increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. It also upregulated mRNA expression of carnitine palmitoyltransferase-1a, suggesting that sinensetin enhances fatty acid ß-oxidation through the AMPK pathway. Taken together, these results suggest that sinensetin may have potential as a natural agent for prevention/improvement of obesity.

Anti-obesity properties of a Sasa quelpaertensis extract in high-fat diet-induced obese mice.

This study explores the anti-obesity properties of a Sasa quelpaertensis leaf extract (SQE) in high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. SQE administration with HFD for 70 d significantly decreased the body weight gain, adipose tissue weight, and serum total cholesterol and triglyceride levels in comparison with the HFD group. SQE administration also reduced the serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactate dehydrogenase, and the accumulation of lipid droplets in the liver, suggesting a protective effect against HFD-induced hepatic steatosis. SQE administration restored the HFD-induced decreases with phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. SQE also induced AMPK phosphorylation in mature 3T3-L1 adipocytes. These results suggest that SQE exerted an anti-obesity effect on HFD-induced obese mice by activating AMPK in adipose tissue and reducing lipid droplet accumulation in the liver.

Immature Citrus sunki peel extract exhibits antiobesity effects by ß-oxidation and lipolysis in high-fat diet-induced obese mice.

The peel of Citrus sunki HORT. ex TANAKA has been widely used in traditional Asian medicine for the treatment of many diseases, including indigestion and bronchial asthma. In this study, we investigated the antiobesity activity of immature C. sunki peel extract (designated CSE) using high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. In the animal study, body weight gain, adipose tissue weight, serum total cholesterol, and triglyceride in the CSE-administered group decreased significantly compared to the HFD group. Also, CSE supplementation reduced serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and lactate dehydrogenase. Moreover, it significantly decreased the accumulation of fatty droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Dietary supplementation with CSE reversed the HFD-induced decrease in the phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which are related to fatty acid ß-oxidation, in the epididymal adipose tissue. Also, CSE increased AMPK and ACC phosphorylation in mature 3T3-L1 adipocytes. CSE also enhanced lipolysis by phosphorylation of cAMP-dependent protein kinase (PKA) and hormone-sensitive lipase (HSL) in mature 3T3-L1 adipocytes. These results suggest that CSE had an antiobesity effect via elevated ß-oxidation and lipolysis in adipose tissue.

A water-soluble extract of Petalonia binghamiae inhibits the expression of adipogenic regulators in 3T3-L1 preadipocytes and reduces adiposity and weight gain in rats fed a high-fat diet.

We previously showed that an ethanolic extract of the edible brown algae Petalonia binghamiae promotes the differentiation of 3T3-L1 preadipocytes and decreases hyperglycemia in streptozotocin-induced diabetic mice. Here, we report that a water-soluble extract of P. binghamiae thalli, prepared by enzymatic digestion, inhibits preadipocyte differentiation and adipogenesis in a dose-dependent manner. In differentiating 3T3-L1 preadipocytes, the extract (designated PBEE) decreased the expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding proteins α and ß, and fatty acid-binding protein aP2. It also inhibited the mitotic clonal expansion process of adipocyte differentiation, and it inhibited insulin-stimulated uptake of glucose into mature 3T3-L1 adipocytes by reducing phosphorylation of insulin receptor substrate-1. In rats with high-fat diet (HFD)-induced obesity, PBEE exhibited potent anti-obesity effects. In this animal model, increases in body weight and fat storage were suppressed by the addition of PBEE to the drinking water at 500 mg/L for 30 days. PBEE supplementation reduced serum levels of glutamic pyruvic and glutamic oxaloacetic transaminases and increased the serum level of high-density lipoprotein cholesterol. Moreover, it significantly decreased the accumulation of lipid droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Taken together, these data demonstrate that PBEE inhibits preadipocyte differentiation and adipogenesis in cultured cells and in rodent models of obesity.