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NHR-49
Journal of Functional Foods · 2025 · IF 4

Sulfated glycosaminoglycan from swim bladder mitigates lipid accumulation in Caenorhabditis elegans by mediating the transcription factor NHR-49

Yehua Huang,Bingbing Song,Zhuo Wang,Kit Leong Cheong,Rui Li,Qiaoli Zhao,Jing Chen,Saiyi Zhong

Sulfated glycosaminoglycan from swim bladder (SBG) is a marine-derived bioactive polysaccharide structurally similar to chondroitin sulfate A. This study investigates the potential of SBG in mitigating hyperlipidemia linked to lipid metabolism disorders. The results indicate that SBG significantly mitigates glucose-induced metabolic disturbances in C. elegans , including reduced fertility, shortened lifespan, elevated ROS levels, lipofuscin accumulation, and impaired antioxidant responses. Notably, at 1 mg/mL, SBG reduced triglyceride and free fatty acid levels by 56.76 % and 26.64 %, respectively ( P  < 0.05), as confirmed by Oil Red O staining. At the molecular level, SBG downregulated the expression of lipid metabolism genes, such as daf-2 , mdt-15 , sbp-1 , and acs-2 . Additionally, SBG upregulated the expression of nhr-49 and daf-16 , which enhanced Δ9-desaturase activity and promoted the synthesis of monounsaturated fatty acids. The deletion of nhr-49 further confirmed that SBG regulates Δ9-desaturase through NHR-49 activation, thereby improving lipid accumulation and preserving metabolic homeostasis.

CAS / MDL: 50-91-9
研究领域: 生物化学 · 分子生物学 · 营养学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 7 ·3048 · IF 4.9

Matrine Inhibits High-Glucose-Diet-Induced Fat Accumulation and Aβ-Mediated Lipid Metabolic Disorder via AAK-2/NHR-49 Pathway in Caenorhabditis elegans

Aimin Qiao,Meiqing Pan,Yue Zeng,Ying Gong,Yunfeng Zhang,Xiucai Lan,Lei Tang,Weizhang Jia

Matrine, a quinoline alkaloid, possesses lipid-regulating effects, but the underlying mechanisms are rarely characterized in vivo. With a fat-accumulating Caenorhabditis elegans model, we show that matrine reduces the fat content and the DHS-3::GFP-labeled lipid droplets in high-glucose-diet N2 and transgenic LIU1 nematodes, respectively. Based on RNA-seq, this study demonstrates that a loss of AAK-2 function suppresses the fat-lowering effects of matrine, and the hyperactivated AAK-2 strain has a relatively lower fat content than N2. The involvement of NHR-49 in matrine’s fat-lowering effects further suggests that matrine impacts fat breakdown and storage via the AAK-2/NHR-49-governed pathway. Using the transgenic SJ4143 ( ges-1::GFP(mit) ) and VS10 ( vha-6p::mRFP-PTS1 ), we show that matrine activates the AAK-2/NHR-49 pathway, coupling the alteration of mitochondrial and peroxisomal functions. Studies of aak-2 and nhr-49 mutants reveal that AAK-2 and NHR-49 modulate lipid metabolic homeostasis; meanwhile, matrine increases physical fitness and lifespan through activating the AAK-2/NHR-49 pathway in high-glucose-diet nematodes. Surprisingly, we found that β-amyloid (Aβ) induces lipid metabolic disorder in an Alzheimer’s disease (AD) C. elegans model, but matrine not only reduces Aβ aggregation but also alleviates Aβ-mediated lipid metabolic disorder. Our data suggest that matrine has promise as a fat-lowering agent, and also offer new insights into its therapeutic potential for AD.

CAS / MDL: 50-91-9 519-02-8
研究领域: 生物化学 · 分子生物学 · 药理学
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Journal of Ginseng Research · 2022 · IF 5.735

Ginsenosides Rg1 regulate lipid metabolism and temperature adaptation in Caenorhabditis elegans

Hao Shi,Jiamin Zhao,Yiwen Li,Junjie Li,Yunjia Li,Jia Zhang,Zhantu Qiu,Chaofeng Wu,Mengchen Qin,Chang Liu,Zhiyun Zeng,Chao Zhang,Lei Gao

Background Obesity is a risk factor for aging and many diseases, and the disorder of lipid metabolism makes it prominent. This study aims to investigate the effect of ginsenoside Rg1 on aging, lipid metabolism and stress resistance Methods Rg1 was administered to Caenorhabditis elegans ( C. elegans ) cultured in NGM or GNGM. The lifespan, locomotory activity, lipid accumulation, cold and heat stress resistance and related mRNA expression of the worms were examined. Gene knockout mutants were used to clarify the effect on lipid metabolism of Rg1. GFP-binding mutants were used to observe the changes in protein expression Results We reported that Rg1 reduced lipid accumulation and improved stress resistance in C. elegans . Rg1 significantly reduced the expression of fatty acid synthesis-related genes and lipid metabolism-related genes in C. elegans . However, Rg1 did not affect the fat storage in fat-5/fat-6 double mutant or nhr-49 mutant. Combined with network pharmacology, we clarified the possible pathways and targets of Rg1 in lipid metabolism. In addition, Rg1-treated C. elegans showed a higher expression of anti-oxidative genes and heat shock proteins, which might contribute to stress resistance Conclusion Rg1 reduced fat accumulation by regulating lipid metabolism via nhr-49 and enhanced stress resistance by its antioxidant effect in C. elegans .

CAS / MDL: 50-99-7
研究领域: 药理学 · 老年学 · 分子生物学 · 遗传学
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