adipogenesis

Adipogenesis, the process of proliferation of adipocyte progenitor cells and their differentiation into mature adipocytes, plays a critical role in the development of obesity. In this context, exploring the effects of phytochemicals on adipogenesis is very promising, as nowadays, they are widely used as food, drink, or supplement and can significantly impact general health and obesity control. This systematic review attempts to evaluate new findings regarding the molecular mechanisms of different phytochemicals on adipogenesis in in vitro models. Between 2010 and July 2023, a comprehensive systematic search of PubMed and Scopus databases was conducted. The following keywords were used: (“adipogenic”) AND (“inhibit” OR “suppress” OR “reduce” OR “anti” OR “decrease”) AND (“cell” OR “cell line” OR “adipocyte”) AND (“phytochemical” OR “plant” OR “herb”). In this review, 109 studies were comprehensively analyzed, which provided important insights into the process of adipogenesis. Among the numerous transcription factors studied, PPARγ, C/EBPα, and SREBP1c were found to be the most important regulators actively involved in adipocyte differentiation. These results highlight the critical role of these factors in the control of adipogenesis and suggest that they represent promising targets for therapeutic interventions aimed at reducing the excessive lipid accumulation associated with obesity. This study provides a compelling rationale for further exploring phytochemicals as potential therapeutics for treating obesity. The potential benefits of using natural products to influence adipogenesis are evident, and future studies should focus on translating these findings into clinical applications.

The leaves of the olive plant (Olea europaea) contain significantly higher levels of phenolic compounds than the fruit and olive oil, acting as a natural supplement for antioxidant activities.

This research aimed to investigate the effect of this extract on certain inflammatory factors (TNF-α, IL-1, IL-6) and its regulatory role on tissue gene (RBP4) in fibroblast cell lines (3T3-L1).

After culturing adipose tissue fibroblast cells (3T3-L1) under sterile and standard conditions, the cells were exposed to different logarithmic concentrations of the extract. The production of inflammatory cytokines TNF-α, IL-1, and IL-6 was measured using ELISA methods, and the expression level of the RBP4 gene was assessed using a real-time PCR technique.

The results showed dose-dependent effects of the extract on the 3T3-L1 cells. The MTT assay indicated that the hydroalcoholic extract of olive plant leaves has a concentration-dependent effect on cell proliferation (∗∗P ≤ 0.05). The DPPH test results showed a significant decrease in the level of active oxygen in the presence of Olive leaf extract (OLE). The catalase and MDA test results also indicated an increase in antioxidant activity in cells treated with the extract. Conversely, the expression levels of inflammatory cytokines IL-1 and IL-6 increased by 0.05 and 0.01 (pg/mL), respectively, while changes in TNF-α and RBP4 gene expression were insignificant (P > 0.05).

The results demonstrated that OLE can enhance the efficiency of antioxidant and inflammatory pathways in the cell and significantly reduce the level of active oxygen in the cell.

Adenoid cystic carcinoma is a slow-growing malignancy that most often occurs in the salivary glands. Currently, no FDA-approved therapeutic target or diagnostic biomarker has been identified for this cancer. The aim of this study was to find new therapeutic and diagnostic targets using bioinformatics methods.

We extracted the gene expression information from two GEO datasets (including GSE59701 and GSE88804). DEGs between ACC and normal samples were extracted using R software. The biochemical pathways involved in ACC were obtained by using the Enrichr database. PPI network was drawn by STRING, and important genes were extracted by Cytoscape. Real-time PCR and immunohistochemistry were used for biomarker verification.

After analyzing the PPI network, 20 hub genes were introduced to have potential as diagnostic and therapeutic targets. Among these genes, PLCG1 was presented as new biomarker in ACC. Furthermore, by studying the function of the hub genes in the enriched biochemical pathways, we found that IGF-1R/IR and PPARG pathways most likely play a critical role in tumorigenesis and drug resistance in ACC and have a high potential for selection as therapeutic targets in future studies.

In this study, we achieved the recognition of the pathways involving in ACC pathogenesis and also found potential targets for treatment and diagnosis of ACC. Further experimental studies are required to confirm the results of this study.

Adipogenesis is affected by multiple factors, among which all-trans retinoic acid (ATRA) and Ca2+are considered important factors.

This study aimed to evaluate the effect of calcium, ATRA, and their underlying molecular mechanisms, alone and in combination, on adipocyte differentiation.

Human adipose-derived mesenchymal stem cells (hAD-MSCs) were differentiated into adipocytes and simultaneously exposed to 0.5 μM ATRA or 2.5 mM calcium, or both in combination for 14 days.

Higher intracellular Ca2+was observed in both Ca2+and Ca2+plus ATRA groups. Assessment of triglyceride content and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) activity indicated lower differentiation levels in all treatment groups than in the control group. Furthermore, the results demonstrated a higher expression of retinoic acid receptor alpha (RAR-α) and lower expression of peroxisome proliferator-activated receptor γ2 (PPARγ2) and glucose transferase-4 (GLUT4) in the treatment groups as compared with the control group. It is noteworthy that Ca2+plus ATRA treatment caused more significant effects on gene expression levels (P<0.05).

In conclusion, combined treatment with Ca2+and ATRA has a more pronounced inhibitory effect on adipocyte differentiation, indicating their cumulative effect.

In this study, we tested the hypothesis that sinapic acid (SA), a naturally occurring hydroxycinnamic acid found in vegetables, cereal grains, and oilseed crops with various biological activities suppresses adipogenesis in 3T3-L1 adipocytes by down-regulating adipogenesis transcription factor. 

3T3-L1 adipocytes were treated with SA and evaluated by Oil Red O staining, triglyceride estimation, lipolysis, and reverse transcription-polymerase chain reaction. 3T3-L1 adipocytes were treated with various concentrations of SA (100 to 1000 μmol) during differentiation. 

SA prevented an increase in adipocytes by reducing preadipocyte clonal expansion. ORO staining analyses revealed that SA reduced cytoplasmic lipid droplet accumulation in 3T3-L1 by 57% at the highest concentration of 1000 μmol without affecting cell viability. Furthermore, SA down-regulated the expression of peroxisome proliferator-activated receptor-gamma, CCAAT/enhancer-binding protein alpha, sterol regulatory element-binding protein 1c, and fatty acid synthase. ROS generated during adipogenesis was also attenuated by SA treatment by increasing antioxidant enzymes superoxide dismutase, catalase, and the cellular antioxidant glutathione. SA demonstrated no in vivo toxicity in the Drosophila melanogaster model. 

These results suggest that SA exerts anti-oxidant and anti-adipogenic effects and could be used as a functional nutraceutical ingredient in combatting obesity-related diseases.

Obesity, often associated with insulin resistance and type 2 diabetes, is a metabolic disease that can result in dyslipidemia and hyperglycemia. Many reports describe the hypoglycemic and hypolipidemic properties of the Phoenix dactylifera L. seed extract in STZ-induced diabetic rat models, however, its anti-diabetic effects in other diabetic models are less characterized in the literature. This study set out to determine the possible effects of the Phoenix dactylifera L. seed extract on adipogenesis and glucose homeostasis.

3T3-L1 cells were cultured in adipocyte differentiation media with or without varying doses of Phoenix dactylifera L. extract (0.312-1 mg/ml). Assays were performed on days 5, 8, and 12 after induced differentiation.

Our results demonstrate that the triglyceride content in treated groups was significantly lower compared to controls. Further, treating 3T3-L1 cells with Phoenix dactylifera L. seed extract reduced adipogenesis through the downregulation of PPAR-γ and CEBP-α, and adipocyte-specific genes involved in fatty acid metabolism including ap2, ACACA, and FAS.

Phoenix dactylifera L. seeds have the potential to inhibit adipogenesis and obesity. Overall, this study explored the inhibitory effects of Phoenix dactylifera L. seed extract on adipogenesis in 3T3-L1 cells on the molecular level.

Natural products have gained importance recently for the treatment of obesity and its complications, partly because of the side effects of modern drugs.Hence, we aimed to study and compare the effect of varying concentrations of Momordicacharantiaon adipogenesis and adipolysis using 3T3-L1 pre-adipocyte cell lines.
3T3-L1 pre-adipocytes were procured from the National Center for Cell Sciences, Pune, and cultured in Dulbecco’s Modified Eagle’s Media (DMEM) supplemented with 20% fetal bovine serum (FBS) and 1 mM L-glutamine. An ethanolic extract of M. charantia (EEMC)was prepared by the graded ethanol fractionation method and the total phenol content (TPC) determined using the Folin-Ciocalteau (F-C) assay. The cytotoxic dose was determined by the sulforhodamine-B (SRB) assay. The adipogenesis and adipolysis assays (Cayman chemicals, Ann Arbor, USA) were performed according to the manufacturer’s protocols.
The 3T3-L1 pre-adipocytes treated with increasing concentrations of EEMC during (p= 0.012) and after (p= 0.026) differentiation demonstrated significant reduction in lipid droplet accumulation. There was a significant decrease in glycerol release during differentiation (p= 0.018) and a significant increase in glycerol release after differentiation (p= 0.0007) with increasing concentrations of EEMC. However, the effect of EEMC on adipogenesis and adipolysis was greater during 3T3-L1 pre-adipocyte differentiation than after.
The data showed that the 50% EEMC is potent inhibitor of lipogenesis and stimulator of lipolysis in 3T3-L1 pre-adipocytes. Further analyses will be performed to determine the key antioxidant compound(s) in the extract by phenolic acid profiling using high performance liquid chromatography (HPLC). Also, the mechanism of action of EEMC on adipogenesis and adipolysis will be elucidated.

Chorisia is an important Bombacaceous plant that is traditionally used for a variety of ailments. Due to its richness in several bioactive phytocompounds, some Chorisia species showed a wide range of important biological effects. Accordingly, the present work was undertaken to comparatively evaluate the antioxidant potential and effects on adipogenesis of Chorisia chodatii Hassl. and Chorisia speciosa A. St.-Hil. in relation to their phenolic contents.  Total polyphenol contents and free radical scavenging potentials of the total ethanol extracts of leaves, flowers, fruits and seeds of both species, in addition to four main fractions of their leaf and flower extracts, were evaluated using the Folin-Ciocalteu's method and the DPPH assay, respectively. Besides, their effects on adipogenesis were studied using the 3T3-L1 preadipocytes model. A phytochemical screening of their different phytoconstituents was also considered.  Total ethanol extracts along with their successive fractions of various parts of both species caused a concentration-dependent induction of 3T3-L1 preadipocytes differentiation, but with a noticeable reduction of the size of the lipid droplets at the lower concentrations 5 and 10 µg/ml. In addition, these extracts showed a strong evidence of their richness in free radical scavengers. The ethyl acetate, aqueous and chloroform fractions of different plant parts exhibited the greatest effects on adipogenesis, substantial free radical scavenging properties and the highest polyphenol contents, respectively. Results collectively revealed that the observed effects of both Chorisia species on adipogenesis as well as their anti-radical properties are positively related to their pool of flavonoids and other phenolics. They also suggest their potential value in obesity-related disorders and for prevention of free radical mediated diseases. Further studies for investigating the molecular basis of their effects on adipogenesis accompanied by detailed phytochemical analysis, especially of their polar and flavonoids-rich extracts, will also be strongly recommended.