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Fulltext Tetracarpidium conophorum nuts (African walnuts) up-regulated adiponectin and PPAR-γ expressions with reciprocal suppression of TNF-α gene in obesity

Umoru GU, Atangwho IJ, David-Oku E, Uti DE, Agwupuye EI, Obeten UN, et al.

J Cell Mol Med, 2024 Dec;28(24):e70086.
PMID: 39698791 DOI: 10.1111/jcmm.70086

Tetracarpidium conophorum nuts are nutrient-dense Nigerian snacks associated with weight regulation. This study explores the nuts' impact on adipose tissue gene expression associated with low-grade inflammation. Ethanol whole extract (EWE), ethyl-acetate fraction (EAF) and the resulting residue (RES) were orally administered once daily to MSG-induced obese rats for 6 weeks (n = 6). Afterward, the RNA synthesis of inflammation-associated genes was measured, and GC-MS ligands in the extract and fractions were docked against their protein products in silico. The study found that in obese animals, PPAR-γ and Adiponectin expressions were down-regulated, while TNF-α was up-regulated, indicating an increased low-grade inflammatory process in adipose tissue. After 6-week oral treatments with EWE, EAF and RES, PPAR-γ and Adiponectin expressions increased significantly, while TNF-α expression decreased, suggesting the modulation of obesity-induced inflammation in adipose tissue. The in silico molecular docking analysis identified four lead compounds likely responsible for the observed effect, namely 6-Isopropenyl-4,8a-dimethyl-4a,5,67,8,8a-hexahydro-1H-naphthalen-2-one, 9,12,15-Octadecatrienoic methyl ester (Z,Z,Z), 9,12,15-Octadecatrienoic acid and Hexanedioic acid, bis(2-ethylhexyl). Of these compounds, 6-Isopropenyl-4,8a-dimethyl-4a,5,67,8,8a-hexahydro-1H-naphthalen-2-one demonstrated the strongest affinity to the binding cavities of PPARγ (-7.3 kcal/mol), Leptin (-5.2 kcal/mol), Adiponectin (-7.1 kcal/mol) and TNF-α (-6.3 kcal/mol) and was better than the standard drug, Orlistat (-6.7, -4.4, -6.8 and - 4.5 kcal/mol, respectively). The study reveals that T. conophorum nuts possess bioactive compounds/drug candidates that can exert positive modulation, at the molecular level, the low-grade inflammatory process associated with obesity, which normally facilitates the outset of complications.

Matched MeSH terms: Adipose Tissue/drug effects
Beneficial metabolic effects of the Malaysian herb Labisia pumila var. alata in a rat model of polycystic ovary syndrome

Mannerås L, Fazliana M, Wan Nazaimoon WM, Lönn M, Gu HF, Ostenson CG, et al.

J Ethnopharmacol, 2010 Feb 3;127(2):346-51.
PMID: 19883744 DOI: 10.1016/j.jep.2009.10.032

New options are needed to prevent and treat metabolic disorders associated with polycystic ovary syndrome (PCOS). Labisia pumila var. alata (LPva)-a Malaysian herb thought to have phytoestrogenic effects-has shown promise in reducing body weight gain in ovariectomized rats. In this study, we investigated the effect of LPva on body composition and metabolic features in female rats treated continuously with dihydrotestosterone, starting before puberty, to induce PCOS.

Matched MeSH terms: Adipose Tissue/drug effects
Fulltext Effects of serum reduction and VEGF supplementation on angiogenic potential of human adipose stromal cells in vitro

Chua KH, Raduan F, Wan Safwani WK, Manzor NF, Pingguan-Murphy B, Sathapan S

Cell Prolif, 2013 Jun;46(3):300-11.
PMID: 23672290 DOI: 10.1111/cpr.12029

OBJECTIVES: This study investigated effects of reduced serum condition and vascular endothelial growth factor (VEGF) on angiogenic potential of adipose stromal cells (ASCs) in vitro.
MATERIALS AND METHODS: Adipose stromal cells were cultured in three different types of medium: (i) F12/DMEM (FD) supplemented with 10% FBS from passage 0 (P0) to P6; (ii) FD supplemented with 2% FBS at P6; and (iii) FD supplemented with 2% FBS plus 50 ng/ml of VEGF at P6. Morphological changes and growth rate of ASCs were recorded. Changes in stemness, angiogenic and endogenic genes' expressions were analysed using Real-Time PCR.
RESULTS: Adipose stromal cells changed from fibroblast-like shape when cultured in 10% FBS medium to polygonal when cultured in 2% FBS plus VEGF-supplemented medium. Their growth rate was lower in 2% FBS medium, but increased with addition of VEGF. Real-Time PCR showed that ASCs maintained most of their stemness and angiogenic genes' expression in 10% FBS at P1, P5 and P6, but this increased significantly in 2% FBS at P6. Endogenic genes expression such as PECAM-1, VE chaderin and VEGFR-2 decreased after serial passage in 10% FBS, but increased significantly at P6 in 2% FBS. Addition of VEGF did not cause any significant change in gene expression level.
CONCLUSION: Adipose stromal cells had greater angiogenic potential when cultured in reduced serum conditions. VEGF did not enhance their angiogenic potential in 2% FBS-supplemented medium.

Matched MeSH terms: Adipose Tissue/drug effects
Fulltext The Beneficial Effects of Stingless Bee Honey from Heterotrigona itama against Metabolic Changes in Rats Fed with High-Carbohydrate and High-Fat Diet

Ramli NZ, Chin KY, Zarkasi KA, Ahmad F

Int J Environ Res Public Health, 2019 12 07;16(24).
PMID: 31817937 DOI: 10.3390/ijerph16244987

Metabolic syndrome (MetS) is a group of conditions including central obesity, hyperglycemia, dyslipidemia, and hypertension that increases the risk for cardiometabolic diseases. Kelulut honey (KH) produced by stingless honey bees has stronger antioxidant properties compared to other honey types and may be a functional food against MetS. This study aimed to determine the efficacy of KH in preventing metabolic changes in rats with MetS induced by high-carbohydrate and high-fat (HCHF) diet. Male Wistar rats were randomly assigned to the control (C), HCHF diet-induced MetS (S), and MetS supplemented with KH (K) groups. The K group was given KH (1 g/kg/day) for eight weeks. Compared to the control, the S group had significant higher omental fat mass, serum triglyceride, systolic blood pressure, diastolic blood pressures, adipocyte area, and adipocyte perimeter (p < 0.05). KH supplementation significantly prevented these MetS-induced changes at week 16 (p < 0.05). Several compounds, including 4-hydroxyphenyl acetic acid, coumaric and caffeic acids, had been detected via liquid chromatography-mass spectrometry analysis that might contribute to the reversal of these changes. The beneficial effects of KH against MetS-induced rats provide the basis for future KH research to investigate its potential use in humans and its molecular mechanisms in alleviating the disease.

Matched MeSH terms: Adipose Tissue/drug effects
Histomorphometric changes in the perirenal adipocytes of adrenalectomized rats treated with dexamethasone

Ahmad F, Soelaiman IN, Ramli ES, Hooi TM, Suhaimi FH

Clinics (Sao Paulo), 2011;66(5):849-53.
PMID: 21789391

INTRODUCTION: Prolonged steroid treatment administered to any patient can cause visceral obesity, which is associated with metabolic disease and Cushing's syndrome. Glucocorticoids have a profound negative effect on adipose tissue mass, giving rise to obesity, which in turn is regulated by the 11β-hydroxysteroid dehydrogenase type 1 enzyme. Adrenalectomized rats treated with dexamethasone exhibited an increase in visceral fat deposition but not in body weight.
OBJECTIVES: The main aim of this study was to determine the effect of dexamethasone on the histomorphometric characteristics of perirenal adipocytes of adrenalectomized, dexamethasone-treated rats (ADR+Dexa) and the association of dexamethasone treatment with the expression and activity of 11 β-hydroxysteroid dehydrogenase type 1 (11 β-hydroxysteroid dehydrogenase type 1).
METHODS: A total of 20 male Sprague Dawley rats were divided into 3 groups: a baseline control group (n = 6), a sham-operated group (n = 7) and an adrenalectomized group (n=7). The adrenalectomized group was given intramuscular dexamethasone (ADR+Dexa) 2 weeks post adrenalectomy, and the rats from the sham-operated group were administered intramuscular vehicle (olive oil).
RESULTS: Treatment with 120 μg/kg intramuscular dexamethasone for 8 weeks resulted in a significant decrease in the diameter of the perirenal adipocytes (p<0.05) and a significant increase in the number of perirenal adipocytes (p<0.05). There was minimal weight gain but pronounced fat deposition in the dexamethasone-treated rats. These changes in the perirenal adipocytes were associated with high expression and dehydrogenase activity of 11β-hydroxysteroid dehydrogenase type 1.
CONCLUSIONS: In conclusion, dexamethasone increased the deposition of perirenal fat by hyperplasia, which causes increases in the expression and dehydrogenase activity of 11 β-hydroxysteroid dehydrogenase type 1 in adrenalectomized rats.

Matched MeSH terms: Adipose Tissue/drug effects
Fulltext Dietary (n-6 : n-3) fatty acids alter plasma and tissue fatty acid composition in pregnant Sprague Dawley rats

Kassem AA, Abu Bakar MZ, Yong Meng G, Mustapha NM

ScientificWorldJournal, 2012;2012:851437.
PMID: 22489205 DOI: 10.1100/2012/851437

The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

Matched MeSH terms: Adipose Tissue/drug effects
Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats

Mashmoul M, Azlan A, Mohtarrudin N, Mohd Yusof BN, Khaza'ai H, Khoo HE, et al.

BMC Complement Altern Med, 2016 Oct 22;16(1):401.
PMID: 27770798

Saffron is the dried stigma of Crocus sativus L. flower which commonly used as a natural remedy to enhance health and even fights disease in the Middle-East and Southeast Asian countries.

Matched MeSH terms: Adipose Tissue/drug effects*
Fulltext Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes

Burgeiro A, Fuhrmann A, Cherian S, Espinoza D, Jarak I, Carvalho RA, et al.

Am J Physiol Endocrinol Metab, 2016 Apr 01;310(7):E550-64.
PMID: 26814014 DOI: 10.1152/ajpendo.00384.2015

Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.

Matched MeSH terms: Adipose Tissue/drug effects
Celastrol attenuates inflammatory responses in adipose tissues and improves skeletal muscle mitochondrial functions in high fat diet-induced obese rats via upregulation of AMPK/SIRT1 signaling pathways

Abu Bakar MH, Shariff KA, Tan JS, Lee LK

Eur J Pharmacol, 2020 Sep 15;883:173371.
PMID: 32712089 DOI: 10.1016/j.ejphar.2020.173371

Accumulating evidence indicates that adipose tissue inflammation and mitochondrial dysfunction in skeletal muscle are inextricably linked to obesity and insulin resistance. Celastrol, a bioactive compound derived from the root of Tripterygium wilfordii exhibits a number of attributive properties to attenuate metabolic dysfunction in various cellular and animal disease models. However, the underlying therapeutic mechanisms of celastrol in the obesogenic environment in vivo remain elusive. Therefore, the current study investigated the metabolic effects of celastrol on insulin sensitivity, inflammatory response in adipose tissue and mitochondrial functions in skeletal muscle of the high fat diet (HFD)-induced obese rats. Our study revealed that celastrol supplementation at 3 mg/kg/day for 8 weeks significantly reduced the final body weight and enhanced insulin sensitivity of the HFD-fed rats. Celastrol noticeably improved insulin-stimulated glucose uptake activity and increased expression of plasma membrane GLUT4 protein in skeletal muscle. Moreover, celastrol-treated HFD-fed rats showed attenuated inflammatory responses via decreased NF-κB activity and diminished mRNA expression responsible for classically activated macrophage (M1) polarization in adipose tissues. Significant improvement of muscle mitochondrial functions and enhanced antioxidant defense machinery via restoration of mitochondrial complexes I + III linked activity were effectively exhibited by celastrol treatment. Mechanistically, celastrol stimulated mitochondrial biogenesis attributed by upregulation of the adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) signaling pathways. Together, these results further demonstrate heretofore the conceivable therapeutic mechanisms of celastrol in vivo against HFD-induced obesity mediated through attenuation of inflammatory response in adipose tissue and enhanced mitochondrial functions in skeletal muscle.

Matched MeSH terms: Adipose Tissue/drug effects*
Molecular mechanism of down-regulating adipogenic transcription factors in 3T3-L1 adipocyte cells by bioactive anti-adipogenic compounds

Guru A, Issac PK, Velayutham M, Saraswathi NT, Arshad A, Arockiaraj J

Mol Biol Rep, 2021 Jan;48(1):743-761.
PMID: 33275195 DOI: 10.1007/s11033-020-06036-8

Obesity is growing at an alarming rate, which is characterized by increased adipose tissue. It increases the probability of many health complications, such as diabetes, arthritis, cardiac disease, and cancer. In modern society, with a growing population of obese patients, several individuals have increased insulin resistance. Herbal medicines are known as the oldest method of health care treatment for obesity-related secondary health issues. Several traditional medicinal plants and their effective phytoconstituents have shown anti-diabetic and anti-adipogenic activity. Adipose tissue is a major site for lipid accumulation as well as the whole-body insulin sensitivity region. 3T3-L1 cell line model can achieve adipogenesis. Adipocyte characteristics features such as expression of adipocyte markers and aggregation of lipids are chemically induced in the 3T3-L1 fibroblast cell line. Differentiation of 3T3-L1 is an efficient and convenient way to obtain adipocyte like cells in experimental studies. Peroxisome proliferation activated receptor γ (PPARγ) and Cytosine-Cytosine-Adenosine-Adenosine-Thymidine/Enhancer-binding protein α (CCAAT/Enhancer-binding protein α or C/EBPα) are considered to be regulating adipogenesis at the early stage, while adiponectin and fatty acid synthase (FAS) is responsible for the mature adipocyte formation. Excess accumulation of these adipose tissues and lipids leads to obesity. Thus, investigating adipose tissue development and the underlying molecular mechanism is important in the therapeutical approach. This review describes the cellular mechanism of 3T3-L1 fibroblast cells on potential anti-adipogenic herbal bioactive compounds.

Matched MeSH terms: Adipose Tissue/drug effects

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