臺灣博碩士論文加值系統

中文摘要 i
Abstract ii
總目錄 iii
圖目錄 ix
表目錄 xii
縮寫表 xiii
第一章、緒論 1
第一節、肥胖 (Obesity) 1
1-1 肥胖之定義 1
1-2 肥胖之成因 2
1-3 肥胖之共病症 2
第二節、脂肪組織 3
2-1 脂肪組織之種類 3
2-1-1 白色脂肪組織 (White adipose tissue, WAT) 4
2-1-2 棕色脂肪組織 (Brown adipose tissue, BAT) 4
2-2 脂肪組織之功能 4
2-2-1 脂肪生成 (Lipogenesis) 5
2-2-2 脂肪分解 (Lipolysis) 6
第三節、脂肪細胞 6
3-1 白色脂肪細胞 (White adipocyte) 7
3-2 棕色脂肪細胞 (Brown adipocyte) 7
3-3 米色脂肪細胞 (Beige adipocyte) 8
第四節、前脂肪細胞 3T3-L1 9
4-1 3T3-L1 細胞之簡介 9
4-2 3T3-L1 細胞之分化機制 9
第五節、脂質奈米微粒 (Lipid nanoparticles) 12
5-1 脂質奈米微粒之優勢 12
5-2 脂質奈米微粒之常見種類 12
5-2-1 固體脂質奈米微粒 (Solid lipid nanoparticles, SLNs) 13
5-2-2 奈米結構脂質載體 (Nanostructured lipid carriers, NLCs) 14
5-3 脂質奈米微粒之口服遞送途徑 16
第六節、共軛亞麻油酸 (Conjugated linoleic acid, CLA) 17
6-1 共軛亞麻油酸之結構 17
6-2 共軛亞麻油酸之食物來源 18
6-2-1 生物合成 18
6-2-2 化學合成 18
6-3 共軛亞麻油酸對體重和體組成之調節 19
6-3-1 CLA 對動物模型肥胖之影響 19
6-3-2 CLA 對人體體重之影響 20
第七節、維生素 E (Vitamin E) 20
7-1 維生素 E 之結構 20
7-2 維生素 E 之食物來源 21
7-3 維生素 E 之儲存器官 22
7-4 維生素 E 之抗氧化功能 22
第二章、研究動機與實驗設計 23
第一節、研究背景與實驗動機 23
第二節、實驗設計與流程 24
第三章、實驗材料與方法 25
第一節、儀器與試劑 25
1-1 儀器 25
1-2 試劑與材料 26
第二節、實驗方法 29
2-1 奈米劑型製備 29
2-1-1 包覆 CLA 之奈米劑型製備 29
2-1-2 染上 Rhodamine 800 之奈米劑型製備 30
2-2 NLCs 奈米劑型物化性質測定 31
2-2-1 劑型之粒徑大小與粒徑分散係數測定 31
2-2-2 劑型之表面電位測定 31
2-3 3T3-L1 細胞培養 32
2-3-1 3T3-L1 細胞之活化 32
2-3-2 3T3-L1 細胞之繼代 32
2-3-3 3T3-L1 細胞之冷凍保存 32
2-3-4 3T3-L1 細胞分化模型建立 33
2-4 體外細胞試驗 34
2-4-1 3T3-L1 脂質堆積實驗模型建立 34
2-4-2 α-Tocopherol、LA、CLA 與包覆 CLA 之奈米劑型對 3T3-L1 細胞之存活率試驗 34
2-4-3 3T3-L1 細胞油紅染色試驗 35
2-4-4 三酸甘油脂 (Triglyceride) 之定量 35
2-4-5 酵素免疫分析法 (Enzyme-linked immunosorbent assay, ELISA) 36
2-4-5-1 TNF-α 定量分析 36
2-4-5-2 IL-6 定量分析 37
2-4-5-3 IL-1β 定量分析 38
2-4-5-4 Leptin 定量分析 38
2-4-6 細胞對於奈米劑型之攝取 39
2-4-6-1 流式細胞分析儀 39
2-4-6-2 正立雷射共軛焦顯微鏡 39
2-4-7 西方墨點法分析 40
2-4-7-1 樣品製備 40
2-4-7-2 電泳膠體製備 40
2-4-7-3 蛋白質電泳 41
2-4-7-4 蛋白質轉漬 41
2-4-7-5 封閉 42
2-4-7-6 一級及二級抗體連接 42
2-4-7-7 ECL 呈色 43
2-5 統計方法 43
第四章、實驗結果 44
第一節、3T3-L1 細胞生長分化 44
第二節、α-Tocopherol 抑制脂質堆積之評估 46
2-1 α-Tocopherol 對 3T3-L1 細胞之存活率試驗 46
2-2 α-Tocopherol 對 3T3-L1 細胞之減脂活性試驗 47
2-2-1 3T3-L1 細胞經 α-tocopherol 處理之油紅染色結果 47
2-2-2 3T3-L1 細胞經 α-tocopherol 處理之 TG 定量結果 48
第三節、CLA 抑制脂質堆積之評估 49
3-1 CLA 及 LA 對 3T3-L1 細胞之存活率試驗 49
3-2 CLA 對 3T3-L1 細胞之減脂活性試驗 51
3-2-1 3T3-L1 細胞經 10 M 之 LA 及 CLA 處理之油紅染色結果 51
3-2-2 3T3-L1 細胞經 50 M 之 LA 及 CLA 處理之油紅染色結果 51
第四節、α-Tocopherol 與 CLA 共同抑制脂質堆積之評估 54
4-1 3T3-L1 細胞經 α-tocopherol 低濃度 10 M 與 CLA 處理之油紅染色結果 54
4-2 3T3-L1 細胞經 α-tocopherol 中濃度 50 M 與 CLA 處理之油紅染色結果 56
4-3 3T3-L1 細胞經 α-tocopherol 高濃度 100 M 與 CLA 處理之油紅染色結果 58
第五節、包覆 CLA 之 NLCs 劑型之物化性質 60
5-1 包覆 CLA 之 NLCs 劑型之粒徑大小、PDI 及 ZP 60
5-2 包覆 CLA 之 NLCs 劑型之安定性 60
第六節、3T3-L1 細胞對於標定 Rhodamine 800 劑型之攝取 62
6-1 流式細胞儀分析細胞攝取之結果 62
6-2 正立雷射共軛焦顯微鏡拍攝細胞攝取之影像 64
第七節、包覆 CLA 之 NLCs 劑型抑制脂質堆積之評估 66
7-1 包覆 CLA 之 NLCs 劑型對 3T3-L1 細胞之存活率試驗 66
7-2 包覆 CLA 之 NLCs 劑型對 3T3-L1 細胞之減脂活性試驗 67
7-2-1 3T3-L1 細胞經包覆 CLA 之 NLCs 劑型處理之油紅染色結果 67
7-2-2 3T3-L1 細胞經包覆 CLA 之 NLCs 劑型處理之 TG 定量結果 70
第八節、包覆 CLA 之 NLCs 劑型對脂肪生成相關蛋白質之影響 71
8-1 3T3-L1 細胞經包覆 CLA 之 NLCs 劑型處理之 PPARγ 的蛋白質表現量 71
8-2 3T3-L1 細胞經包覆 CLA 之 NLCs 劑型處理之 C/EBPα 的蛋白質表現量 73
第九節、包覆 CLA 之 NLCs 劑型之抗發炎活性分析 75
9-1 3T3-L1 細胞經包覆 CLA 之 NLCs 劑型處理之 TNF-α 釋放量 75
9-2 3T3-L1 細胞經包覆 CLA 之 NLCs 劑型處理之 IL-6 釋放量 77
9-3 3T3-L1 細胞經包覆 CLA 之 NLCs 劑型處理之 IL-1β 釋放量 78
第十節、包覆 CLA 之 NLCs 劑型對 leptin 之影響 79
第五章、綜合討論 80
第六章、結論 86
第七章、參考文獻 88
附錄 99

 
圖目錄
圖一、脂肪組織之示意圖 3
圖二、脂肪組織之脂質代謝 5
圖三、白色、棕色及米色脂肪細胞之間的型態差異 6
圖四、脂肪細胞之生命週期 10
圖五、3T3-L1 細胞分化過程中的基因表現 11
圖六、SLNs 和 NLCs 之結構 (a) SLNs 之結構 (b) NLCs 之結構 13
圖七、SLNs 及 NLCs 之載藥量差異 14
圖八、NLCs 之三種型態 15
圖九、LA 及 CLA 異構體之結構 17
圖十、維生素 E 之異構體 21
圖十一、3T3-L1 細胞分化流程 33
圖十二、第 8 天之 3T3-L1 細胞生長分化情形 45
圖十三、α-Tocopherol 對 3T3-L1 細胞之存活率 46
圖十四、不同濃度之 α-tocopherol 對 3T3-L1 細胞內油滴生成之第 8 天油紅染色圖 47
圖十五、α-Tocopherol 對 3T3-L1 細胞之第 8 天油滴累積量化圖 48
圖十六、3T3-L1 細胞經不同濃度之 α-tocopherol 處理後之 TG 含量 49
圖十七、CLA 及 LA 對 3T3-L1 細胞之存活率 50
圖十八、濃度 10 M 之 LA 及 CLA 對 3T3-L1 細胞內油滴生成之第 8 天油紅染色圖 52
圖十九、濃度 10 M 之 LA 及 CLA 對 3T3-L1 細胞之第 8 天油滴累積量化圖 52
圖二十、濃度 50 M 之 LA 及 CLA 對 3T3-L1 細胞內油滴生成之第 8 天油紅染色圖 53
圖二十一、濃度 50 M 之 LA 及 CLA 對 3T3-L1 細胞之第 8 天油滴累積量化圖 53
圖二十二、α-Tocopherol 10 M 與 CLA 之組合對 3T3-L1 細胞內油滴生成之第 8 天油紅染色圖 55
圖二十三、α-Tocopherol 10 M 與 CLA 之組合對 3T3-L1 細胞之第 8 天油滴累積量化圖 55
圖二十四、α-Tocopherol 50 M 與 CLA 之組合對 3T3-L1 細胞內油滴生成之第 8 天油紅染色圖 56
圖二十五、α-Tocopherol 50 M 與 CLA 之組合對 3T3-L1 細胞之第 8 天油滴累積量化圖 57
圖二十六、α-Tocopherol 100 M 與 CLA 之組合對 3T3-L1 細胞內油滴生成之第 8 天油紅染色圖 58
圖二十七、α-Tocopherol 100 M 與 CLA 之組合對 3T3-L1 細胞之第 8 天油滴累積量化圖 59
圖二十八、細胞攝取奈米劑型之流式細胞儀檢測結果 63
圖二十九、3T3-L1 細胞攝取奈米劑型之正立雷射共軛焦顯微鏡影像 65
圖三十、三種包覆 CLA 之 NLCs 劑型對 3T3-L1 細胞之存活率 66
圖三十一、三種包覆 CLA 之 NLCs 劑型對 3T3-L1 細胞內油滴生成之第 8 天油紅染色圖 68
圖三十二、三種包覆 CLA 之 NLCs 劑型對分化前 3T3-L1 細胞之第 8 天油滴累積量化圖 69
圖三十三、3T3-L1 細胞經三種包覆 CLA 之 NLCs 劑型處理之 TG 含量 70
圖三十四、包覆 CLA 之 NLCs 對 PPARγ 的蛋白質表現量 72
圖三十五、包覆 CLA 之 NLCs 對 C/EBPα 的蛋白質表現量 74
圖三十六、包覆 CLA 之 NLCs 劑型對 TNF-α 之釋放量 76
圖三十七、包覆 CLA 之 NLCs 劑型對 IL-6 之釋放量 77
圖三十八、包覆 CLA 之 NLCs 劑型對 IL-1β 之釋放量 78
圖三十九、包覆 CLA 之 NLCs 劑型對 leptin 之釋放量 79
 
表目錄
表一、WHO 與我國之肥胖標準 1
表二、包覆 CLA 之奈米劑型處方比例 30
表三、電泳膠體之製備配方 41
表四、一級抗體反應條件 42
表五、二級抗體反應條件 42
表六、包覆 CLA 之 NLCs 劑型之粒徑大小、PDI 及 ZP 61

Aaseth, J., Ellefsen, S., Alehagen, U., Sundfor, T.M., Alexander, J., 2021. Diets and drugs for weight loss and health in obesity-an update. Biomed. Pharmacother. 140, 111789.
Alexander, H.R., Syed Alwi, S.S., Yazan, L.S., Zakarial Ansar, F.H., Ong, Y.S., 2019. Migration and proliferation effects of thymoquinone-loaded aanostructured lipid carrier (TQ-NLC) and thymoquinone (TQ) on in vitro wound healing models. Evid.-based Complement Altern. Med. 29, 9725738.
Alkhouri, N., Lawitz, E., Noureddin, M., DeFronzo, R., Shulman, G.I., 2020. GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH). Expert Opin. Investig. Drugs 29, 135–141.
Arroyo Hornero, R., Hamad, I., Côrte-Real, B., Kleinewietfeld, M., 2020. The impact of dietary components on regulatory T cells and disease. Front. Immunol. 21, 253.
Azzi, A., 2021. Reflections on a century of vitamin E research: looking at the past with an eye on the future. Free Radic. Biol. Med. 175, 155–160.
Bahari, L.A.S., Hamishehkar, H., 2016. The impact of variables on particle size of solid lipid nanoparticles and nanostructured lipid carriers; a comparative literature review. Adv. Pharm. Bull. 6, 143–151.
Balamurugan, K., Chintamani, P., 2018. Lipid nano particulate drug delivery: an overview of the emerging trend. J. Pharm. Innov. 7, 779–789.
Baraldi, F., Dalalio, F., Teodoro, B., Prado, I., Curti, C., Alberici, L., 2014. Body energy metabolism and oxidative stress in mice supplemented with conjugated linoleic acid (CLA) associated to oleic acid. Free Radic. Biol. Med. 75, 21–53.
Basak, S., Duttaroy, A.K., 2020. Conjugated linoleic acid and its beneficial effects in obesity, cardiovascular disease, and cancer. Nutrients 12, 1913.
Birringer, M., Lorkowski, S., 2019. Vitamin E: regulatory role of metabolites. IUBMB Life 71, 479–486.
Bittar, R., Aslangul, E., Giral, P., Assoumou, L., Valantin, M.A., Kalmykova, O., 2017. Lack of effects of statins on high-density lipoprotein subfractions in HIV-1-infected patients receiving protease inhibitors. C. R. Biol. 340, 109–113.
Borges, A., Freitas, V., Mateus, N., Fernandes, I., Oliveira, J., 2020. Solid lipid nanoparticles as carriers of natural phenolic compounds. Antioxidants 9, 998–1021.
Borrelli, M.R., Patel, R.A., Sokol, J., Nguyen, D., Momeni, A., Longaker, M.T., Wan, D.C., 2019. Fat chance: the rejuvenation of irradiated skin. PRS-GLOB. OPEN 7, 2092–2099.
Boughanem, H., Cabrera-Mulero, A., Millán-Gómez, M., Garrido-Sánchez, L., Cardona, F., Tinahones, F.J., Macías-González, M., 2019. Transcriptional analysis of FOXO1, C/EBP-α and PPAR-γ2 genes and their association with obesity-related insulin resistance. Genes 10, 706.
Burdeos, G.C., Nakagawa, K., Abe, T., Kimura, F., Miyazawa, T., 2014. Tocotrienol modulates crucial lipid metabolism-related genes in differentiated 3T3-L1 preadipocytes. Food Funct. 5, 2221–2227.
Caballero, B., 2019. Humans against obesity: who will win? Adv. Nutr. 10, 4–9.
Chang, Y., Noh, J.W., Cheon, J.Y., Kim, Y., Kwon, Y.D., Ryu, S., 2020. Self-rated health and risk of incident non-alcoholic fatty liver disease: a cohort study. Sci. Rep. 10, 3826–3833.
Cisneros-Zevallos, L., Bang, W.Y., Delgadillo-Puga, C., 2020. Ellagic acid and urolithins A and B differentially regulate fat accumulation and inflammation in 3T3-L1 adipocytes while not affecting adipogenesis and insulin sensitivity. Int. J. Mol. Sci. 21, 2086–2101.
Costa, A.M.M., Gaspar, B.R.A., Calado, V., Tonon, R.V., Torres, A.G., 2022. Microencapsulation of pomegranate (Punica granatum L.) seed oil by complex coacervation: Stability and application in an instant caffè latte beverage. Food Chem. 381, 132199.
Da Silva, C., Durandt, C., Kallmeyer, K., Ambele, M.A., Pepper, M.S., 2020. The role of pref-1 during adipogenic differentiation: an overview of suggested mechanisms. Int. J. Mol. Sci. 21, 4104–4129.
De Lorenzo, A., Gratteri, S., Gualtieri, P., Cammarano, A., Bertucci, P., Di Renzo, L., 2019. Why primary obesity is a disease? J. Transl. Med. 17, 169–181.
Den Hartigh, L.J., 2019. Conjugated linoleic acid effects on cancer, obesity, and atherosclerosis: a review of pre-clinical and human trials with current perspectives. Nutrients 11, 370–398.
Dhiman, N., Awasthi, R., Sharma, B., Kharkwal, H., Kulkarni, G.T., 2021. Lipid nanoparticles as carriers for bioactive delivery. Front. Chem. 9, 580118.
Dilzer, A., Park, Y., 2012. Implication of conjugated linoleic acid (CLA) in human health. Crit. Rev. Food Sci. Nutr. 52, 488–513.
Dipasquale, D., Basiricò, L., Morera, P., Primi, R., Tröscher, A., Bernabucci, U., 2018. Anti-inflammatory effects of conjugated linoleic acid isomers and essential fatty acids in bovine mammary epithelial cells. Animal 12, 2108–2114.
Dowey, R., Iqbal, A., Heller, S.R., Sabroe, I., Prince, L.R., 2021. A bittersweet response to infection in diabetes; targeting neutrophils to modify inflammation and improve host immunity. Front. Immunol. 12, 678771.
Endalifer, M.L., Diress, G., 2020. Epidemiology, predisposing factors, biomarkers, and prevention mechanism of obesity: a systematic review. J. Obes. 2020, 1–8.
Fuke, G., Nornberg, J.L., 2017. Systematic evaluation on the effectiveness of conjugated linoleic acid in human health. Crit. Rev. Food Sci. Nutr. 57, 1–7.
Funk, M.I., Conde, M.A., Piwien-Pilipuk, G., Uranga, R.M., 2021. Novel antiadipogenic effect of menadione in 3T3-L1 cells. Chem.-Biol. Interact. 343, 109491.
Gallelli, C.A., Calcagnini, S., Romano, A., Koczwara, J.B., De Ceglia, M., Dante, D., Gaetani, S., 2018. Modulation of the oxidative stress and lipid peroxidation by endocannabinoids and their lipid analogues. Antioxidants 7, 93–136.
Gammone, M.A., D'Orazio, N., 2021. COVID-19 and obesity: overlapping of two pandemics. Obes. Facts 14, 579–585.
Goossens, G.H., 2017. The metabolic phenotype in obesity: fat mass, body fat distribution, and adipose tissue function. Obes. Facts 10, 207–215.
Guru, A., Issac, P.K., Velayutham, M., Saraswathi, N.T., Arshad, A., Arockiaraj, J., 2021. Molecular mechanism of down-regulating adipogenic transcription factors in 3T3-L1 adipocyte cells by bioactive anti-adipogenic compounds. Mol. Biol. Rep. 48, 743–761.
Hashemi, F.S., Farzadnia, F., Aghajani, A., Ahmadzadeh NobariAzar, F., Pezeshki, A., 2020. Conjugated linoleic acid loaded nanostructured lipid carrier as a potential antioxidant nanocarrier for food applications. Food Sci. Nutr. 8, 4185–4195.
Hirata, B.K.S., Cruz, M.M., De Sa, R., Farias, T.S.M., Machado, M.M.F., Bueno, A.A., Telles, M.M., 2019. Potential anti-obesogenic effects of Ginkgo biloba observed in epididymal white adipose tissue of obese rats. Front. Endocrinol. 10, 284–294.
Hou, W., Chen, Q., Wang, H., Qiu, P., Lyu, X., Chen, W., Wang, R., 2020. The metabolic footprint during adipocyte commitment highlights ceramide modulation as an adequate approach for obesity treatment. EBioMedicine 51, 1–15.
Ikeda, K., Maretich, P., Kajimura, S., 2018. The common and distinct features of brown and beige adipocytes. Trends Endocrinol. Metab. 29, 191–200.
Jeong, Y.U., Park, Y.J., 2020. Ergosterol peroxide from the medicinal mushroom Ganoderma Iucidum inhibits differentiation and lipid accumulation of 3T3-L1 adipocytes. Int. J. Mol. Sci. 21, 1–13.
Jerome, G.J., Ko, S.U., Chiles Shaffer, N.S., Studenski, S.A., Ferrucci, L., Simonsick, E.M., 2016. Cross-sectional and longitudinal associations between adiposity and walking endurance in adults age 60-79. J. Gerontol. A Biol. Sci. Med. Sci. 71, 1661–1666.
Jiang, Q., 2014. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic. Biol. Med. 72, 76–90.
Juretic, N., Sepulveda, R., D'Espessailles, A., Vera, D.B., Cadagan, C., De Miguel, M., Tapia, G., 2021. Dietary alpha- and gamma-tocopherol (1:5 ratio) supplementation attenuates adipose tissue expansion, hepatic steatosis, and expression of inflammatory markers in a high-fat-diet-fed murine model. Nutrition 85, 111139.
Kersten, S., 2014. Physiological regulation of lipoprotein lipase. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1841, 919–933.
Khosa, A., Reddi, S., Saha, R.N., 2018. Nanostructured lipid carriers for site-specific drug delivery. Biomed. Pharmacother. 103, 598–613.
Kim, D., Park, J.H., Kweon, D.J., Han, G.D., 2013. Bioavailability of nanoemulsified conjugated linoleic acid for an antiobesity effect. Int. J. Nanomed. 8, 451–459.
Kiyose, C., Takeuchi, H., Yabe, Y., Nojima, T., Nagase, M., Takahashi-Muto, C., Tanaka-yachi, R., 2021. Effect of δ-tocopherol on mice adipose tissues and mice adipocytes induced inflammation. J. Oleo Sci. 70, 1307–1315.
Koohikamali, S., Kamal, S.M.M., 2015. Enhanced oxidative stability and water miscibility of conjugated linoleic acid complexed with lysine and arginine. Eur. J. Lipid Sci. Technol. 117, 637–645.
Kowalska, K., Olejnik, A., 2016. Cranberries (Oxycoccus quadripetalus) inhibit pro-inflammatory cytokine and chemokine expression in 3T3-L1 adipocytes. Food Chem. 196, 1137–1143.
Krstic, J., Reinisch, I., Schupp, M., Schulz, T.J., Prokesch, A., 2018. p53 Functions in adipose tissue metabolism and homeostasis. Int. J. Mol. Sci. 19, 2622–2642.
Kumari Ramiah, S., Meng, G.Y., Ebrahimi, M., 2014. Dietary conjugated linoleic acid alters oxidative stability and alleviates plasma cholesterol content in meat of broiler chickens. Sci. World J. 2014, 1–10.
Kuri-Harcuch, W., Velez-delValle, C., Vazquez-Sandoval, A., Hernandez-Mosqueira, C., Fernandez-Sanchez, V., 2019. A cellular perspective of adipogenesis transcriptional regulation. J. Cell. Physiol. 234, 1111–1129.
Lee, G.Y., Han, S.N., 2018. The role of vitamin E in immunity. Nutrients 10, 1614–1631.
Lehnen, T.E., Da Silva, M.R., Camacho, A., Marcadenti, A., Lehnen, A.M., 2015. A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism. J. Int. Soc. Sport Nutr. 12, 36–46.
Li, H., Zhuang, P., Zhang, Y., Shou, Q., Lu, Y., Wang, G., Jiao, J., 2021. Mixed conjugated linoleic acid sex‐dependently reverses high‐fat diet‐induced insulin resistance via the gut‐adipose axis. Faseb J. 35, e21466.
Li, T., Zhang, L., Jin, C., Xiong, Y., Cheng, Y.Y., Chen, K., 2020. Pomegranate flower extract bidirectionally regulates the proliferation, differentiation and apoptosis of 3T3-L1 cells through regulation of PPARγ expression mediated by PI3K-AKT signaling pathway. Biomed. Pharmacother. 131, 110769.
Liu, L., Li, Y., Tollefsbol, T.O., 2008. Gene-environment interactions and epigenetic basis of human diseases. Curr. Issues Mol. Biol. 10, 25–36.
Lizcano, F., 2019. The beige adipocyte as a therapy for metabolic diseases. Int. J. Mol. Sci. 20, 1–25.
Luo, L., Liu, M., 2016. Adipose tissue in control of metabolism. J. Endocrinol. 231, 77–99.
Majima, D., Mitsuhashi, R., Yamasaki, M., Kajimoto, K., Fukuta, T., Kogure, K., 2021. Suppression of lipid accumulation in 3T3-L1 adipocytes by α-tocopheryl succinate. Biol. Pharm. Bull. 44, 46–50.
Martins, S.V., Madeira, A., Lopes, P.A., Pires, V.M., Alfaia, C.M., Prates, J. A., Soveral, G., 2015. Adipocyte membrane glycerol permeability is involved in the anti-adipogenic effect of conjugated linoleic acid. Biochem. Biophys. Res. Commun. 458, 356–361.
Morrison, S., McGee, S.L., 2015. 3T3-L1 adipocytes display phenotypic characteristics of multiple adipocyte lineages. Adipocyte 4, 295–302.
Moseti, D., Regassa, A., Kim, W.K., 2016. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int. J. Mol. Sci. 17, 124–147.
Ntambi, J.M., Young-Cheul, K., 2000. Adipocyte differentiation and gene expression. J. Nutr. 130, 3122–3126.
Park, A., Kim, W.K., Bae, K.H., 2014. Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells. World J. Stem Cells 6, 33–42.
Park, W.Y., Choe, S.K., Park, J., Um, J.Y., 2019. Black raspberry (Rubus coreanus Miquel) promotes browning of preadipocytes and inguinal white adipose tissue in cold-induced mice. Nutrients 11, 2164–2178.
Parray, H.A., Yun, J.W., 2016. Cannabidiol promotes browning in 3T3-L1 adipocytes. Mol. Cell. Biochem. 416, 131–139.
Peng, J., Li, K., Zhu, W., Nie, R., Wang, R., Li, C., 2019. Penta-O-galloyl-β-d-glucose, a hydrolysable tannin from Radix Paeoniae Alba, inhibits adipogenesis and TNF-α-mediated inflammation in 3T3-L1 cells. Chem.-Biol. Interact. 302, 156–163.
Qadir, A., Liang, S., Wu, Z., Chen, Z., Hu, L., Qian, A., 2020. Senile osteoporosis: the involvement of differentiation and senescence of bone marrow stromal cells. Int. J. Mol. Sci. 21, 349–371.
Qayum, A., Li, M., Shi, R., Bilawal, A., Gantumur, M.A., Hussain, M., Ishfaq, M., Waqas Ali Shah, S., Jiang, Z., Hou, J., 2021. Laccase cross-linking of sonicated α-Lactalbumin improves physical and oxidative stability of CLA oil in water emulsion. Ultrason. Sonochem. 71, 105365.
Racine, N.M., Watras, A.C., Carrel, A.L., Allen, D.B., McVean, J.J., Clark, R.R., Schoeller, D.A., 2010. Effect of conjugated linoleic acid on body fat accretion in overweight or obese children. Am. J. Clin. Nutr. 91, 1157–1164.
Rajbhandari, P., Arneson, D., Hart, S.K., Ahn, I.S., Diamante, G., Santos, L.C., Vergnes, L., 2019. Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes. eLife 8, 1–57.
Rayalam, S., Della-Fera, M.A., Baile, C.A., 2008. Phytochemicals and regulation of the adipocyte life cycle. J. Nutr. Biochem. 19, 717–726.
Rodrigo, N., Glastras, S.J., 2018. The emerging role of biomarkers in the diagnosis of gestational diabetes mellitus. J. Clin. Med. 7, 120–135.
Rojas, M.M., Villalpando, D.M., Alexander-Aguilera, A., Ferrer, M., García, H.S., 2021. Effect of CLA supplementation on factors related to vascular dysfunction in arteries of orchidectomized rats. Prostaglandins Other Lipid Mediat. 157, 106586.
Rosenwald, M., Wolfrum, C., 2014. The origin and definition of brite versus white and classical brown adipocytes. Adipocyte 3, 4–9.
Ruban, A., Stoenchev, K., Ashrafian, H., Teare, J., 2019. Current treatments for obesity. J. Clin. Med. 19, 205–212.
Savonen, R., Hiden, M., Hultin, M., Zechner, R., Levak-Frank, S., Olivecrona, G., Olivecrona, T., 2015. The tissue distribution of lipoprotein lipase determines where chylomicrons bind. J. Lipid Res. 56, 588–598.
Scheja, L., Heeren, J., 2019. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat. Rev. Endocrinol. 15, 507–524.
Scioli Montoto, S., Muraca, G., Ruiz, M.E., 2020. Solid lipid nanoparticles for drug delivery: pharmacological and biopharmaceutical aspects. Front. Mol. Biosci. 7, 1–24.
Selvamuthukumar, S., Velmurugan, R., 2012. Nanostructured lipid carriers: a potential drug carrier for cancer chemotherapy. Lipids Health Dis. 11, 1–8.
Sen, C.K., Khanna, S., Roy, S., 2007. Tocotrienols in health and disease: the other half of the natural vitamin E family. Mol. Asp. Med. 28, 692–728.
Severino, P., Andreani, T., Macedo, A.S., Fangueiro, J.F., Santana, M.H., Silva, A.M., Souto, E.B., 2012. Current state-of-art and new trends on lipid nanoparticles (SLN and NLC) for oral drug delivery. J. Drug Deliv. 2012, 1–10.
Shahmirzadi, F.E., Ghavamzadeh, S., Zamani, T., 2019. The effect of conjugated linoleic acid supplementation on body composition, serum insulin and leptin in obese adults. Arch. Iran. Med. 22, 255.
Shen, W., Chuang, C.C., Martinez, K., Reid, T., Brown, J.M., Xi, L., McIntosh, M., 2013. Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice. J. Lipid Res. 54, 909–922.
Shen, W., McIntosh, M.K., 2016. Nutrient regulation: conjugated linoleic acid's inflammatory and browning properties in adipose tissue. Annu. Rev. Nutr. 36, 183–210.
Shinn, S.E., Ruan, C.M., Proctor, A., 2017. Strategies for producing and incorporating conjugated linoleic acid-rich oils in foods. Annu. Rev. Food Sci. Technol. 8, 181–204.
Shokryzadan, P., Rajion, M.A., Meng, G.Y., Boo, L.J., Ebrahimi, M., Royan, M., Jahromi, M.F., 2017. Conjugated linoleic acid: a potent fatty acid linked to animal and human health. Crit. Rev. Food Sci. Nutr. 57, 2737–2748.
Talegaonkar, S., Bhattacharyya, A., 2019. Potential of lipid nanoparticles (SLNs and NLCs) in enhancing oral bioavailability of drugs with poor intestinal permeability. AAPS PharmSciTech 20, 121–135.
Traber, M.G., 2014. Vitamin E inadequacy in humans: causes and consequences. Adv. Nutr. 5, 503–514.
Wallace, M., Metallo, C.M., 2020. Tracing insights into de novo lipogenesis in liver and adipose tissues. Semin. Cell Dev. Biol. 108, 65–71.
Wang, G., Meyer, J.G., Cai, W., Softic, S., Li, M.E., Verdin, E., Kahn, C.R., 2019. Regulation of UCP1 and mitochondrial metabolism in brown adipose tissue by reversible succinylation. Mol. Cell 74, 844–857.
Whelan, J., Fritsche, K., 2013. Linoleic acid. Adv. Nutr. 4, 311–312.
Wu, L.Y., Chen, C.W., Chen, L.K., Chou, H.Y., Chang, C.L., Juan, C.C., 2019. Curcumin attenuates adipogenesis by inducing preadipocyte apoptosis and inhibiting adipocyte differentiation. Nutrients 11, 2307–2329.
Zhang, L., Zhang, L., Wang, X., Si, H., 2017. Anti-adipogenic effects and mechanisms of ginsenoside Rg3 in pre-adipocytes and obese mice. Front. Pharmacol. 8, 113–122.