Protective Effect of Perilla Oil Against Dextran Sodium Sulfate-Induced Colitis in Mice Challenged with a High-Fat Diet.

This study investigated the effect of perilla oil (PO) on an ulcerative colitis mouse model. Five-week-old male C57BL/6J mice were divided into HD (high-fat diet control), HDD (high-fat diet along with dextran sodium sulfate [DSS] administration), HDD + FO, HDD + PO, and HDD + OO where HDD + FO, HDD + PO, and HDD + OO groups were treated with fish oil (FO), PO, and olive oil (OO), respectively. Biochemical analysis of serum, quantitative polymerase chain reaction, and western blotting of colon tissue were conducted to measure inflammatory marker levels. Administration of DSS resulted in colon shortening and a higher disease activity score than HD group. These symptoms were significantly reversed in the oil-treated groups. The body weight loss after DSS administration was significantly lower in the HDD + PO and HDD + OO groups than in the HDD and HDD + FO groups. PO significantly attenuated the levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß in the serum and colon. The mRNA expression levels of proinflammatory markers in the colon were reduced, whereas those of tight junction proteins and epithelial defense barrier-associated markers were increased by PO treatment. The protein expression of p-p65 was significantly lower in the PO-treated group than the HDD group. In summary, this study revealed that PO improved colitis in the DSS-induced mouse model, indicating its potential role in managing conditions such as ulcerative colitis.

Green perilla leaf extract ameliorates long-term oxidative stress induced by a high-fat diet in aging mice.

BACKGROUND/OBJECTIVES: Oxidative stress is caused by an imbalance between harmful free radicals and antioxidants. Long-term oxidative stress can lead to an "exhausted" status of antioxidant defense system triggering development of metabolic syndrome and chronic inflammation. Green perilla (Perilla frutescens) is commonly used in Asian cuisines and traditional medicine in southeast Asia. Green perilla possesses numerous beneficial effects including anti-inflammatory and antioxidant functions. To investigate the potentials of green perilla leaf extract (PE) on oxidative stress, we induced oxidative stress by high-fat diet (HFD) in aging mice. MATERIALS/METHODS: C57BL/6J male mice were fed HFD continuously for 53 weeks. Then, mice were divided into three groups for 12 weeks: a normal diet fed reference group (NDcon), high-fat diet fed group (HDcon), and high-fat diet PE treated group (HDPE, 400 mg/kg of body weight). Biochemical analyses of serum and liver tissues were performed to assess metabolic and inflammatory damage and oxidative status. Hepatic gene expression of oxidative stress and inflammation related enzymes were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: PE improved hepatopathology. PE also improved the lipid profiles and antioxidant enzymes, including hepatic glutathione peroxidase (GPx) and superoxide dismutase (SOD) and catalase (CAT) in serum and liver. Hepatic gene expressions of antioxidant and anti-inflammatory related enzymes, such as SOD-1, CAT, interleukin 4 (IL-4) and nuclear factor erythroid 2-related factor (Nrf2) were significantly enhanced by PE. PE also reduced the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in the serum and liver; moreover, PE suppressed hepatic gene expression involved in pro-inflammatory response; Cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). CONCLUSIONS: This research opens opportunities for further investigations of PE as a functional food and possible anti-aging agent due to its attenuative effects against oxidative stress, resulting from HFD and aging in the future.

Protective Effect of Diet-Supplemented and Endogenously Produced Omega-3 Fatty Acids against HFD-Induced Colon Inflammation in Mice.

Perilla (Perilla frutescens) oil reduces high-fat-diet-induced colon inflammation by suppressing the NF-κB pathway. In the current study, we compared the effect of endogenously produced and externally supplemented omega-3 fatty acids on high-fat-diet-induced colon inflammation. The fat-1 transgenic mice that endogenously synthesize omega-3 fatty acids were backcrossed with C57BL/6J wild-type mice to obtain transgenic (TR) and wild-type (WT) littermates. Five-week-old male littermates were divided into five groups: two groups fed 10% normal diet (WTLD, TRLD) and three groups fed with a 60% fat high-fat diet (WTHD, TRHD, and WTPO). In the WTPO group, 8% (w/w) of perilla oil was added. Perilla oil supplemented WT mice and fat-1 transgenic mice suppressed high-fat-diet-induced body weight and improved serum lipid levels. Furthermore, the WTPO and TRHD groups exhibited increased colon length, lower macroscopic scores, and reduced levels of pro-inflammatory markers and improved epithelial integrity barrier markers. The expression of GPR120 was increased in the WTPO group. Altogether, our results indicated that perilla oil could improve the symptoms of colon inflammation as an alternate omega-3 fatty acid supplement.

Inhibitory effect of ethanolic extract of Abeliophyllum distichum leaf on 3T3-L1 adipocyte differentiation.

BACKGROUND/OBJECTIVES: Abeliophyllum distichum is a plant endemic to Korea, containing several beneficial natural compounds. This study investigated the effect of A. distichum leaf extract (ALE) on adipocyte differentiation. MATERIALS/METHODS: The cytotoxic effect of ALE was analyzed using cell viability assay. 3T3-L1 preadipocytes were differentiated using induction media in the presence or absence of ALE. Lipid accumulation was confirmed using Oil Red O staining. The mRNA expression of adipogenic markers was measured using RT-PCR, and the protein expressions of mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor gamma (PPARγ) were measured using western blot. Cell proliferation was measured by calculating the incorporation of Bromodeoxyuridine (BrdU) into DNA. RESULTS: ALE reduced lipid accumulation in differentiated adipocytes, as indicated by Oil Red O staining and triglyceride assays. Treatment with ALE decreased the gene expression of adipogenic markers such as Pparγ, CCAAT/enhancer binding protein alpha (C/ebpα), lipoprotein lipase, adipocyte protein-2, acetyl-CoA carboxylase, and fatty acid synthase. Also, the protein expression of PPARγ was reduced by ALE. Treating the cells with ALE at different time points revealed that the inhibitory effect of ALE on adipogenesis is higher in the early period treatment than in the terminal period. Furthermore, ALE inhibited adipocyte differentiation by reducing the early phase of adipogenesis and mitotic clonal expansion. This was indicated by the lower number of cells in the Synthesis phase of the cell cycle (labeled using BrdU assay) and a decrease in the expression of early adipogenic transcription factors such as C/ebpß and C/ebpδ. ALE suppressed the phosphorylation of MAPK, confirming that the effect of ALE was through the suppression of early phase of adipogenesis. CONCLUSIONS: Altogether, the results of the present study revealed that ALE inhibits lipid accumulation and may be a potential agent for managing obesity.

Dietary Iron Deficiency Modulates Adipocyte Iron Homeostasis, Adaptive Thermogenesis, and Obesity in C57BL/6 Mice.

BACKGROUND: Adaptive thermogenesis is an iron-demanding pathway, significantly contributing to whole-body energy expenditure. However, the effects of iron-deficient diets on adaptive thermogenesis and obesity remain unknown. OBJECTIVES: We aimed to determine the impact of dietary iron deficiency on iron homeostasis in adipocytes, adaptive thermogenic capacity, and metabolic consequences in obesity. METHODS: C57BL/6 male mice were assigned to either the iron-adequate (IA, 35 ppm) or the iron-deficient group (ID, 3 ppm) at weaning. Upon 8 wk of age, both IA and ID groups received an isocaloric high-fat diet (45% kcal from fat) for 10 wk, maintaining the same iron content. Mice (n = 8) were used to determine the iron status at the systemic and tissue levels and lipid metabolism and inflammatory signaling in adipose tissue. The same mice were used to evaluate cold tolerance (4°C) for 3 h. For assessing adaptive thermogenesis, mice (n = 5) received an intraperitoneal injection of ß3-adrenoceptor agonist CL316243 (CL) for 5 d. RESULTS: Compared with the IA group, the ID group had nonanemic iron deficiency, lower serum ferritin (42.8%, P < 0.01), and greater weight gain (8.67%, P < 0.05) and insulin resistance (159%, P < 0.01), partly due to reduced AMP-activated protein kinase activation (61.0%, P < 0.05). Upon cold exposure, the ID group maintained a core body temperature 2°C lower than the IA group. The ID group had lower iron content (47.0%, P < 0.01) in the inguinal adipose tissue (iWAT) than the IA group, which was associated with impaired adaptive thermogenesis. In response to CL, ID mice showed decreased heat production (P < 0.01) and defective upregulation of beige adipocyte-specific markers, including uncoupling protein 1 (41.1%, P < 0.001), transferrin receptor 1 (47.5%, P < 0.001), and mitochondrial respiratory chain complexes (P < 0.05) compared with IA mice. CONCLUSIONS: Dietary iron deficiency deregulates iron balance in the iWAT and impairs adaptive thermogenesis, thereby escalating the diet-induced weight gain in C57BL/6 mice.

Anti-Obesity Effects of Morus alba L. and Aronia melanocarpa in a High-Fat Diet-Induced Obese C57BL/6J Mouse Model.

The present study investigated the synergic effect of extracts of Morus alba (MA) and Aronia melanocarpa (Michx.) (AR) against high-fat diet induced obesity. Four-week-old male C57BL/6J mice were randomly divided into five groups that were fed for 14 weeks with a normal diet (ND), high-fat diet (HD), HD with M. alba 400 mg/kg body weight (MA), HD with A. melanocarpa 400 mg/kg body weight (AR), or HD with a mixture (1:1, v/v) of M. alba and A. melanocarpa (400 mg/kg) (MA + AR). Treatment with MA, AR, and MA + AR for 14 weeks reduced high fat diet-induced weight gain and improved serum lipid levels, and histological analysis revealed that MA and AR treatment markedly decreased lipid accumulation in the liver and adipocyte size in epididymal fat. Furthermore, micro-CT images showed MA + AR significantly reduced abdominal fat volume. Expression levels of genes involved in lipid anabolism, such as SREBP-1c, PPAR-γ, CEBPα, FAS, and CD36 were decreased by MA + AR treatment whereas PPAR-α, ACOX1, and CPT-1a levels were increased by MA + AR treatment. Protein expression of p-AMPK and p-ACC were increased in the MA + AR group, indicating that MA + AR ameliorated obesity by upregulating AMPK signaling. Together, our findings indicate that MA and AR exert a synergistic effect against diet-induced obesity and are promising agents for managing obesity.

Abeliophyllum distichum Ameliorates High-Fat Diet-Induced Obesity in C57BL/6J Mice by Upregulating the AMPK Pathway.

The use of natural compounds as anti-obesity agents has been gaining attention over the past few years. Abeliophyllum distichum Nakai is endemic to Korea. In the present study, an A. distichum leaf extract (AE) was analyzed for its anti-obesity effects in mice fed a high-fat diet. Seven-week-old male C57BL/6J mice were divided into five groups, namely, normal diet (ND), high-fat diet (HD), HD + Garcinia (GE300), HD + AE low dose (AE100), and HD + AE high dose (AE300). After 8 weeks of the experimental period, treatment with AE reduced body weight and ameliorated high-fat diet-induced changes in serum lipid levels. Histological analysis revealed that treatment with AE decreased lipid accumulation in the liver and brown adipose tissue. Also, AE reduced the adipocyte size in epididymal fat. The reduction in adipose tissue mass in the AE-treated groups was clearly visible in micro-computed tomography images. The expression levels of lipogenic genes, such as PPARγ, C/EBPα, ACC, and FAS, were significantly reduced in the AE300 group. The levels of p-AMPK and p-ACC were increased in the AE300 group compared to the HD group, indicating that the anti-obesity effect of AE was mediated through the AMPK pathway.

Effect of vegetable oils with different fatty acid composition on high-fat diet-induced obesity and colon inflammation.

BACKGROUND/OBJECTIVES: Different fatty acids exert different health benefits. This study investigated the potential protective effects of perilla, olive, and safflower oils on high-fat diet-induced obesity and colon inflammation. MATERIALS/METHODS: Five-week old, C57BL/6J mice were assigned to 5 groups: low-fat diet (LFD), high-fat diet (HFD) and high-fat diet supplemented with-perilla oil (HPO), olive oil (HOO), and safflower oil (HSO). After 16 weeks of the experimental period, the mice were sacrificed, and blood and tissues were collected. The serum was analyzed for obesity- and inflammation-related biomarkers. Gene expression of the biomarkers in the liver, adipose tissue, and colon tissue was analyzed. Micro-computed tomography (CT) analysis was performed one week before sacrifice. RESULTS: Treatment with all the three oils significantly improved obesity-induced increases in body weight, liver weight, and epididymal fat weight as well as serum triglyceride and leptin levels. Treatment with perilla oil (PO) and safflower oil (SO) increased adiponectin levels. The micro-CT analysis revealed that PO and SO reduced abdominal fat volume considerably. The mRNA expression of lipogenic genes was reduced in all the three oil-supplemented groups and PO upregulated lipid oxidation in the liver. Supplementation of oils improved macroscopic score, increased colon length, and decreased serum endotoxin and proinflammatory cytokine levels in the colon. The abundance of Bifidobacteria was increased and that of Enterobacteriaceae was reduced in the PO-supplemented group. All three oils reduced proinflammatory cytokine levels, as indicated by the mRNA expression. In addition, PO increased the expression of tight junction proteins. CONCLUSIONS: Taken together, our data indicate that the three oils exert similar anti-obesity effects. Interestingly, compared with olive oil and SO, PO provides better protection against high-fat diet-induced colon inflammation, suggesting that PO consumption helps manage inflammation-related diseases and provides omega-3 fatty acids needed by the body.

Perilla Oil Alleviates High-Fat Diet-Induced Inflammation in the Colon of Mice by Suppressing Nuclear Factor-Kappa B Activation.

This study aimed to evaluate the effect of perilla oil (PO) on high-fat diet (HD)-induced colonic inflammation. Male C57BL/6J mice (5 weeks old) were divided into four groups: normal diet, HD, HD supplemented with fish oil (FO), and HD supplemented with PO, and were fed experimental diets for 16 weeks. PO significantly ameliorated (P < .05) the HD-induced colon inflammation as indicated by the increased colon length and low macroscopic score. PO increased the number of Bifidobacteria and reduced the number of Enterobacteriaceae, which in turn resulted in the lowering of endotoxin levels. Proinflammatory cytokines in serum and colon such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α were also decreased by PO treatment. In addition, PO suppressed the expression of cyclooxygenase 2 and inducible nitric oxide, and inhibited the activation of nuclear factor-κB in the colon while increasing the expression of the tight junction protein, Zonula occludens-1. The gene expression of GPR120, a membrane receptor activated by omega-3 fatty acids, was increased in the oil-treated groups. Altogether, PO improved HD-induced colon inflammatory conditions, and the effects were similar to those of FO, confirming that PO is a potential omega-3 fatty acid source for dietary supplements.

Antiobesity Effects of Purple Perilla (Perilla frutescens var. acuta) on Adipocyte Differentiation and Mice Fed a High-fat Diet.

Purple perilla (PE) is a medicinal plant that has several health benefits. In this study, the antiobesity effect of PE was studied in 3T3-L1 preadipocytes and C57BL/6J mice fed high-fat diets. Triglyceride quantification and Oil Red O staining in matured adipocytes revealed that PE reduced lipid accumulation in differentiated adipocytes by downregulating adipogenic gene and upregulating lipolytic gene expressions. Mice were fed normal diet, high-fat diet and high-fat diet supplemented with different concentrations of PE. Treatment with PE significantly prevented body weight gain, improved serum lipids, hepatic lipids and reduced the epididymal fat. Furthermore, in the adipose tissue and liver, expression of genes related to lipolysis and fatty acid ß-oxidation were upregulated in PE- treated mice. Thus, our results suggested that PE has antiobesity effects in rodents and can be effective in obesity management. PRACTICAL APPLICATION: Purple perilla, rich in polyphenols such as rosmarinic acid, showed lipid lowering in adipocyte cells and prevented body weight gain in mice. Therefore we conclude that purple perilla may be a potential candidate for the development of functional foods or nutraceuticals in managing obesity in humans.

Strategic Design and Fabrication of Biomimetic 3D Scaffolds: Unique Architectures of Extracellular Matrices for Enhanced Adipogenesis and Soft Tissue Reconstruction.

The higher rate of soft tissue impairment due to lumpectomy or other trauma greatly requires the restoration of the irreversibly lost subcutaneous adipose tissues. The nanofibers fabricated by conventional electrospinning provide only a superficial porous structure due to its sheet like 2D structure and thereby hinder the cell infiltration and differentiation throughout the scaffolds. Thus we developed a novel electrospun 3D membrane using the zwitterionic poly (carboxybetaine-co-methyl methacrylate) co-polymer (CMMA) through electrostatic repulsion based electrospinning for soft tissue engineering. The inherent charges in the CMMA will aid the nanofiber to directly transform into a semiconductor and thereby transfer the immense static electricity from the grounded collector and will impart greater fluffiness to the scaffolds. The results suggest that the fabricated 3D nanofiber (CMMA 3NF) scaffolds possess nanofibers with larger inter connected pores and less dense structure compared to the conventional 2D scaffolds. The CMMA 3NF exhibits significant cues of soft tissue engineering such as enhanced biocompatibility as well as the faster regeneration of cells. Moreover the fabricated 3D scaffolds greatly assist the cells to develop into its stereoscopic topographies with an enhanced adipogenic property.