In the present study, we investigated the anti-obesity effects of LN19183, a combination of extracts of Citrus aurantifolia fruit rind and Theobroma cacao seed, in vitro and in vivo. Oil Red O staining and Western blotting were performed on 3T3-L1 adipocytes to examine the inhibitory effects on lipid accumulation and the underlying mechanisms. Additionally, LN19183, along with a high-fat diet, was administered to rats for 28 days, and body weight and serum biochemical profiles were assessed. In vitro study results showed that LN19183 significantly reduced lipid accumulation in a dose-dependent manner. Moreover, treatment with LN19183 regulated the expression of markers of adipogenesis (PPAR-γ, C/EBPβ, SREBP-1, FABP4, FAS), lipolysis (ACYL, PPARα, CPT-1), and thermogenesis (PGC-1, UCP-1) by adiponectin, leptin, AMPK, and ACC. In vivo, LN19183 administration significantly reduced body weight, serum triglycerides, leptin, glucose and adipose weight. Our study was the first to reveal the anti-obesity effects of LN19183 through adipogenesis and lipolysis, supporting its potential as a nutraceutical for reducing body fat.
EnginA. The definition and prevalence of obesity and metabolic syndrome. Adv Exp Med Biol, 2017; 960:1–17; doi: 10.1007/978-3-319-48382-5_1
2.
JeongSM, JungJH, YangYS, et al.; Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity. 2023 Obesity Fact Sheet: Prevalence of obesity and abdominal obesity in adults, adolescents, and children in Korea from 2012 to 2021. J Obes Metab Syndr, 2024; 33(1):27–35; doi: 10.7570/jomes24012
3.
MasoodB, MoorthyM. Causes of obesity: A review. Clin Med (Lond), 2023; 23(4):284–291; doi: 10.7861/clinmed.2023-0168
ChanY, NgSW, TanJZX, et al.Natural products in the management of obesity: Fundamental mechanisms and pharmacotherapy. S Afr J Bot, 2021; 143:176–197; doi: 10.1016/j.sajb.2021.07.026
6.
MosetiD, RegassaA, KimWK. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int J Mol Sci, 2016; 17(1):124; doi: 10.3390/ijms17010124
7.
BougarneN, WeyersB, DesmetSJ, et al.Molecular actions of PPARα in lipid metabolism and inflammation. Endocr Rev, 2018; 39(5):760–802; doi: 10.1210/er.2018-00064
8.
ChengY, LiangS, ZhangS, et al.Thermogenic fat as a new obesity management tool: From pharmaceutical reagents to cell therapies. Biomedicines, 2024; 12(7):1474; doi: 10.3390/biomedicines12071474
9.
AmmatalliNKR, KurichetiSSSK, VeeramachaneniS, et al.A combination of Citrus aurantifolia fruit rind and Theobroma cacao seed extracts supplementation enhances metabolic rates in overweight subjects: A randomized, placebo-controlled, cross-over study. Food Nutr Res, 2024; 68:10.29219/fnr.v68.10745; doi: 10.29219/fnr.v68.10745
10.
Rabadan-ChávezG, Quevedo-CoronaL, GarciaAM, et al.Cocoa powder, cocoa extract and epicatechin attenuate hypercaloric diet-induced obesity through enhanced β-oxidation and energy expenditure in white adipose tissue. J Funct Foods, 2016; 20:54–67; doi: 10.1016/j.jff.2015.10.016
11.
AhmadF, KartonoA, SukmawatiSU, et al.Antioxidant activity of flavonoid compounds in lime (Citrus aurantifolia) via density functional theory. 2023; doi: 10.21203/rs.3.rs-3438370/v1
12.
IgbayilolaYD, GremaMG, JibrinS. Molecular docking assessment of cocoa bean flavonoid extract and its impact on lipase enzymes and blood markers in high-fat diet fed rats. Food and Humanity, 2024; 3:100443; doi: 10.1016/j.foohum.2024.100443
13.
BarrHG, McCrackenKJ. High efficiency of energy utilisation in “cafeteria” and force-fed rats kept at 29°C. Brit J Nutr, 1984:51379–51387.
14.
WilcoxRR, KeselmanHJ. Modern robust data analysis methods: Measures of central tendency. Psychol Methods, 2003; 8(3):254–274; doi: 10.1037/1082-989x.8.3.254
15.
CheungBMY, CheungTT, SamaranayakeNR. Safety of antiobesity drugs. Ther Adv Drug Saf, 2013; 4(4):171–181; doi: 10.1177/2042098613489721
16.
LoizzoMR, TundisR, BonesiM, et al.Evaluation of Citrus aurantifolia peel and leaves extracts for their chemical composition, antioxidant and anti-cholinesterase activities. J Sci Food Agric, 2012; 92(15):2960–2967; doi: 10.1002/jsfa.5708
17.
CastellanosJM, QuinteroCS, CarrenoR. Changes on chemical composition of cocoa beans due to combined convection and infrared radiation on a rotary dryer. IOP Conf Ser: Mater Sci Eng, 2018; 437:012011; doi: 10.1088/1757-899x/437/1/012011
18.
LiaoJ-T, HuangY-W, HouC-Y, et al.D-Limonene promotes anti-obesity in 3T3-L1 adipocytes and high-calorie diet-induced obese rats by activating the AMPK signaling pathway. Nutrients, 2023; 15(2):267; doi: 10.3390/nu15020267
19.
SuiGG, XiaoHB, LuXY, et al.Naringin activates AMPK resulting in altered expression of SREBPs, PCSK9, and LDLR To reduce body weight in obese C57BL/6J mice. J Agric Food Chem, 2018; 66(34):8983–8990; doi: 10.1021/acs.jafc.8b02696
20.
JangMH, KangNH, MukherjeeS, et al.Theobromine, a methylxanthine in cocoa bean, stimulates thermogenesis by inducing white fat browning and activating brown adipocytes. Biotechnol Bioproc E, 2018; 23(6):617–626; doi: 10.1007/s12257-018-0434-y
21.
KundimiS, ChintaG, AlluriKV, et al.A synergistic botanical composition increases resting energy expenditure and reduces adiposity in high-fat diet-fed rats. 2023; doi: 10.1080/27697061.2023.2280777
22.
JungHK, JeongYS, ParkCD, et al.Inhibitory Effect of citrus peel extract on lipid accumulation of 3T3-L1 adipocytes. J Korean Soc Appl Biol Chem, 2011; 54(2):169–176; doi: 10.3839/jksabc.2011.028
23.
Clemente-SuárezVJ, Redondo-FlórezL, Beltrán-VelascoAI, et al.The role of adipokines in health and disease. Biomedicines, 2023; 11(5):1290; doi: 10.3390/biomedicines11051290
24.
WangMY, LeeY, UngerRH. Novel form of lipolysis induced by leptin. J Biol Chem, 1999; 274(25):17541–17544; doi: 10.1074/jbc.274.25.17541
25.
GibyVG, AjithTA. Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease. World J Hepatol, 2014; 6(8):570–579; doi: 10.4254/wjh.v6.i8.570
26.
AtsushiS, MasayukiN, SatoshiO, et al.Heptamethoxyflavone inhibits adipogenesis via enhancing PKA signaling. Eur J Pharmacol, 2019; 865:172758; doi: 10.1016/j.ejphar.2019.172758
27.
AhmadB, SerpellCJ, FongIL, et al.Molecular mechanisms of adipogenesis: The anti-adipogenic role of AMP-activated protein kinase. Front Mol Biosci, 2020; 7:76; doi: 10.3389/fmolb.2020.00076
28.
NguyenVTT, VuVV, PhamPV. Brown adipocyte and browning thermogenesis: Metabolic crosstalk beyond mitochondrial limits and physiological impacts. Adipocyte, 2023; 12(1):2237164; doi: 10.1080/21623945.2023.2237164
29.
LeTDV, FathiP, WattersAB, et al.Fibroblast growth factor-21 is required for weight loss induced by the glucagon-like peptide-1 receptor agonist liraglutide in male mice fed high carbohydrate diets. Mol Metab, 2023; 72:101718; doi: 1016/j.molmet.2023.101718
30.
LiH, DonelanW, WangF, et al.GLP-1 induces the expression of FNDC5 derivatives that execute lipolytic actions. Front Cell Dev Biol, 2021; 9:777026; doi: 10.3389/fcell.2021.777026
31.
WangJ-Y, WangQ-W, YangX-Y, et al.GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach. Front Endocrinol (Lausanne), 2023; 14:1085799; doi: 10.3389/fendo.2023.1085799
32.
YangJ, RenJ, SongJ, et al.Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes. Int J Mol Med, 2013; 31(6):1429–1435; doi: 10.3892/ijmm.2013.1350
33.
BuT, SunZ, PanY, et al.Glucagon-like peptide-1: New regulator in lipid metabolism. Diabetes Metab J, 2024; 48(3):354–372; doi: 10.4093/dmj.2023.0277
34.
MelhornSJ, KrauseEG, ScottKA, et al.Acute exposure to a high-fat diet alters meal patterns and body composition. Physiol Behav, 2010; 99(1):33–39; doi: 10.1016/j.physbeh.2009.10.004
