Frontiers in Marine Science
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2024
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IF 2.8
Cui Kun,Zhang Hanle,Yun Biao,Wang Jianxue,Qian Xueqiao,Xue Min
We investigated the effects of dietary supplementation with sodium propionate (SP) and tributyrin (TB) on hepatic lipid deposition and antioxidant capacity of spotted seabass (Lateolabrax maculatus) via an 8-week feeding experiment and a hypoxia stress experiment. The fish were fed five experimental diets: a control diet (CON), a diet supplemented with 2 g/kg SP (SP-0.2%), 4 g/kg SP (SP-0.4%), 2 g/kg TB (TB-0.2%), or 4 g/kg TB (TB-0.4%). No significant difference in growth performance was presented among the groups (P > 0.05). The SP-0.4% and TB-0.2% groups presented significantly lower hepatosomatic and viscerasomatic indexes compared with the CON group. Then, the SP-0.4% and TB-0.2% groups presented stronger resistance to hypoxic stress than the other groups and were analyzed further. The hepatic histology and triglyceride levels revealed that SP-0.4% and TB-0.2% reduced hepatic lipid deposition. Similarly, the downregulation of malondialdehyde and the upregulation of total antioxidant capacity, superoxide dismutase, and catalase activities and the related gene expression levels revealed that SP-0.4% and TB-0.2% improved the antioxidant capacity. Additionally, the RNA sequencing demonstrated that SP-0.4% and TB-0.2% regulated gene expression to a similar extent. Among the 117 differentially expressed genes, 67 genes were enriched in the same pattern, and involved the FoxO signaling, PI3K-Akt signaling, and insulin-related pathways. In conclusion, supplementing SP-0.4% and TB-0.2% as feed additives effectively improved hepatic lipid metabolism, antioxidant capacity, and hypoxic stress resistance of spotted seabass.
研究领域:
水产养殖
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营养学
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分子生物学
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生理学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Lin Yanting,Gao Rui,Jing Dongquan,Liu Yiming,Da Huijuan,Birnbaumer Lutz,Yang Yong,Gao Xinghua,Gao Zhenhua,Cao Qiuhua
During the past half-century, although numerous interventions for obesity have arisen, the condition’s prevalence has relentlessly escalated annually. Obesity represents a substantial public health challenge, especially due to its robust correlation with co-morbidities, such as colorectal cancer (CRC), which often thrives in an inflammatory tumor milieu. Of note, individuals with obesity commonly present with calcium and vitamin D insufficiencies. Transient receptor potential canonical (TRPC) channels, a subclass within the broader TRP family, function as critical calcium transporters in calcium-mediated signaling pathways. However, the exact role of TRPC channels in both obesity and CRC pathogenesis remains poorly understood. This study set out to elucidate the part played by TRPC channels in obesity and CRC development using a mouse model lacking all seven TRPC proteins (TRPC HeptaKO mice). Relative to wild-type counterparts, TRPC HeptaKO mice manifested severe obesity, evidenced by significantly heightened body weights, augmented weights of epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), increased hepatic lipid deposition, and raised serum levels of total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C). Moreover, TRPC deficiency was accompanied by an decrease in thermogenic molecules like PGC1-α and UCP1, alongside a upsurge in inflammatory factors within adipose tissue. Mechanistically, it was revealed that pro-inflammatory factors originating from inflammatory macrophages in adipose tissue triggered lipid accumulation and exacerbated obesity-related phenotypes. Intriguingly, considering the well-established connection between obesity and disrupted gut microbiota balance, substantial changes in the gut microbiota composition were detected in TRPC HeptaKO mice, contributing to CRC development. This study provides valuable insights into the role and underlying mechanisms of TRPC deficiency in obesity and its related complication, CRC. Our findings offer a theoretical foundation for the prevention of adverse effects associated with TRPC inhibitors, potentially leading to new therapeutic strategies for obesity and CRC prevention.
研究领域:
免疫学
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内分泌学
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肿瘤学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2025
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IF 3.6
Yujing Wang,Yuanxin Xu,Yilin Liu,Jindan Lin,Xincai Hong,Shuang Yan
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global disease with a broad spectrum of symptoms. Pirin (PIR) is involved in a variety of biological and molecular processes. However, the role of PIR in MASLD remains unclear. Rats were fed with high-fat and high-cholesterol (HFC) diet to induce MASLD. Time-course results showed that liver in HFC-fed rats exhibited a progressive increase in hepatic tissue damage over time (3, 6, and 9 weeks), and developed in obvious hepatic fibrosis and steatosis at week 9. Meanwhile, HFC feeding also gradually increased PIR expression in liver. In vitro , PIR expression was up-regulated in palmitic acid (PA)-induced Hep3B cells. PIR knockdown using PIR shRNA plasmid inhibited steatosis and expression of ACLY, FASN, and XBP1 in PA-induced Hep3B cells. Knocking down PIR inhibited hepatocyte inflammation by inhibiting phosphor-NF-κB p65 into the nucleus, which inhibited the expression of TNF-α and IL-1β. In MASLD, hepatocyte inflammation activates hepatic stellate cell, thereby leading to hepatic fibrosis. Supernatant from PA-treated Hep3B with PIR knockdown inhibited LX-2 activation, as evidenced by decreased expression of Col1A1 and α-SMA in LX-2 cells. Together, these results suggested that PIR knockdown might alleviate the progression of MASLD by inhibiting liver lipid deposition and inflammation, further inhibiting liver fibrosis. Transcriptome data analysis suggested that alteration in the expression of lipid metabolism-related pathways and genes might be a potential cause of PIR regulation in MASLD progression. These findings may reveal a novel target for MASLD therapy.
研究领域:
分子生物学
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肝病学
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代谢疾病
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细胞生物学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Yufeng Dai,Jinxiang Chen,Jialong Fang,Shuxiao Liang,Hao Zhang,Haitao Li,Wei Chen
Thromboxane A 2 (TXA 2 ) is traditionally known for its role in inducing platelet aggregation, but our previous study has discovered its crucial involvement in hepatic glucolipid metabolism and adipose tissue inflammation. Ginkgolide B (GB), a naturally occurring terpene lactone, possesses various pharmacological functions through its antagonism of the platelet activating factor (PAF) receptor. However, the metabolic regulation mechanism link between the anti-obesity efficiency of GB and TXA 2 has remained elusive. Therefore, this research aimed to explore the potential of GB in protecting against obesity by inhibiting TXA 2 synthesis. The results showed that GB inhibited TXA 2 biosynthesis which shares a similar action with eicosapentaenoic acid (EPA) and aspirin. GB treatment ameliorated hyperglycemia by decreasing gluconeogenesis. Additionally, GB supplementation relieved hepatic lipid deposition and dyslipidemia. Furthermore, GB intervention promoted macrophage M2 polarization, thus mitigating adipose tissue inflammation. In summary, our study provided evidence that GB alleviated glucolipid metabolism disorders and adipose tissue inflammation through the inhibition of the TXA 2 pathway. These findings shed light on the mechanism underlying the anti-obesity efficacy of GB and lay foundations for the future use of GB as a functional dietary supplement to alleviate high-fat diet-induced obesity.
研究领域:
药理学
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代谢
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炎症
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营养
✓ 已验证
产品关联
DOI
高影响因子
Drug Design Development and Therapy
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2023
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IF 4.8
Ning Zhang,Tong Liu,Jianan Wang,Yingying Xiao,Ying Zhang,Jun Dai,Zhihong Ma,Donglai Ma
Background Metabolic associated fatty liver disease (MAFLD) is a chronic disease characterized by excessive lipid deposition in the liver without alcohol or other clear liver-damaging factors. AMP-activated protein kinase (AMPK)/silencing information regulator (SIRT)1 signaling pathway plays an important role in MAFLD development. Si-Ni-San (SNS), a traditional Chinese medicine, has shown reducing hepatic lipid deposition in MAFLD rats, however, the underlying mechanisms of SNS are barely understood.Purpose The aim of this research was to investigate the mechanisms of SNS in reducing hepatic lipid deposition in MAFLD rats by regulating AMPK/SIRT1 signaling pathways.Methods The components of SNS were determined by high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis. MAFLD rats were induced by high-fat and high-cholesterol diet (HFHCD), and treated by SNS. SNS-containing serum and Compound C (AMPK inhibitor) were used to treat palmitic acid (PA)-induced HepG2 cells. To elucidate the potential mechanism, lipid synthesis-related proteins (SREBP-1c and FAS), fatty acid oxidation (PPARα and CPT-1), and AMPK/SIRT1 signaling pathway (p-AMPK and SIRT1) were assessed by Western blot.Results SNS improved serum lipid levels, liver function and reduced hepatic lipid deposition in MAFLD rats. SNS-containing serum reduced lipid deposition in PA-induced HepG2 cells. SNS could up-regulate protein expressions of PPARα, CPT-1, p-AMPK and SIRT1, and down-regulate protein expressions of SREBP-1c and FAS. Similar effects of SNS-containing serum were observed in PA-induced HepG2 cells. Meanwhile, Compound C weakened the therapeutic effects of SNS-containing serum on lipid deposition.Conclusion SNS could reduce hepatic lipid deposition by inhibiting lipid synthesis and promoting fatty acid oxidation, which might be related with activating the AMPK/SIRT1 signaling pathway. This study could provide a theoretical basis for the clinical use of SNS to treat MAFLD.
研究领域:
药理学
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肝病学
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中医药
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Bobo Li,Jie Liu,Yuhui Sun,Mengmeng Song,Xiaoming Zhao,Yulan Sun
Metabolic disturbances associated with obesity increase the risk and advancement of various tumor forms, including postmenopausal lung cancer, in humans. Betaxanthin, a type of yellow-orange pigment found in certain plants, particularly in some flowers, fruits, and vegetables, can be utilized to inhibit the growth of tumors and lessen the metabolic dysfunctions brought on by obesity. However, the functional role of betaxanthin (BET) in suppressing lung cancer progression and its potential mechanisms are still not fully understood. In this study, we examined the regulation of BET in obese mice with postmenopausal lung cancer receiving a high-fat diet (HFD). Initially, we found that BET could significantly mitigate the metabolic dysfunction that a high-fat diet causes in mice. Improved histological changes in the mammary fat pad, lower hepatic lipid deposition, and improved glucose tolerance and insulin resistance demonstrated this. Following that, BET treatment inhibited the formation of lung neoplasms in in-situ cancer animal models that were stimulated by HFD. Furthermore, in a postmenopausal mouse model fed HFD, BET significantly reduced the growth of pre-existing lung tumors, as well as attenuating metabolic abnormalities. Notably, in vitro research revealed that BET co-culture significantly reduced the proliferation and migration of mouse lung cancer cells, whereas insulin exposure increased these processes. Research on animals verified that lung cancer progressed due to hyperinsulinemia; however, BET treatment might inhibit this condition in postmenopausal mice on a high-fat diet. BET could up-regulate sirtuin 3 (SIRT3) expression levels in tumor, liver, and mammary fat pad tissues in postmenopausal mice with HFD-induced obesity, according to a bioinformatic and molecular biology study. Crucially, eradicating SIRT3 expression completely eliminated BET’s inhibitory effects on insulin-stimulated cancer cell proliferation and migration. This suggests that increasing SIRT3 expression may be required for BET to perform its anti-tumor function against lung cancer in conditions of hyperinsulinemia. Our findings showed that by modifying SIRT3 signaling, BET consumption is probably effective in the prevention and treatment of obesity-related lung cancer.
研究领域:
肿瘤学
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代谢学
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药理学
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分子生物学
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生物信息学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Shuwei Ke,Siyu Zhang,Dongsheng Liu,Tengjiao Zhao,Xiayan Lou,Sunying Cheng,Tingheng Zhu,Hanbing Li
Ectopic olfactory receptors, such as OR1A1, are involved in the regulation of lipid metabolism homeostasis. In this study, we investigated the effects of three monoterpenes, (+)-limonene, (−)-carvone and thymol, upon hepatic lipid deposition. Oral administration of (+)-limonene, (−)-carvone and thymol for 8 weeks in high-fat-diet (HFD)-fed mice significantly lowered the levels of fasting blood glucose, improved glucose intolerance, serum lipid parameters, adiposity, and hepatic steatosis. In LO2 cells, (+)-limonene, (−)-carvone and thymol increased the cyclic adenosine monophosphate (cAMP), induced protein kinase A (PKA) activity and phosphorylation of AMPK, downregulated the expression of SREBP-1 and FASN, and eventually led to a reduction in hepatic lipid deposition. Meanwhile, these beneficial effects in cultured LO2 cells were negated by OR1A1 knockdown and the adenylyl cyclase inhibitor SQ22536, respectively, indicating that they can ameliorate disorders of lipid metabolism through activating OR1A1 and subsequent AMPK/SREBP-1/FASN pathway, indicating OR1A1 as a potential target for counteracting hepatic steatosis.
研究领域:
药理学
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代谢学
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肝病学
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分子生物学
✓ 已验证
DOI
高影响因子
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