Low circulating dihomo-gamma-linolenic acid is associated with diabetic retinopathy: a cross sectional study of KAMOGAWA-DM cohort study

Okamura, Tomio; Nakajima, Harushi; Hashimoto, Yoshitaka; Majima, Susumu; Senmaru, Takafumi; Ushigome, Emi; Nakanishi, Naoko; Hamaguchi, Masahide; Asano, Mai; Yamazaki, Masahiro; Takakuwa, Hiroshi; Fukui, Michiaki

doi:10.1507/endocrj.ej20-0564

Cited by 9 publications

(5 citation statements)

References 47 publications

(38 reference statements)

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“…In RT-PCR analyses, the expression of genes involved in the inflammatory response, such as Tnfa, Il6, and Il1b, and fibrosis, such as Col1a, in the liver of the FFD group was significantly higher than that of the ND group, whereas that of the PHGG group was significantly lower than that of the FFD group ( Supplementary Figure S1D–G ). On the other hand, the expression of the IL-22 gene, a cytokine which is downstream of ILC3 and reported to ameliorate liver damage in NAFLD [ 34 , 35 , 36 ], was significantly decreased in the FFD group compared to the ND group, whereas it was significantly increased in the PHGG group ( Supplementary Figure S1H ). Moreover, the expression of Tnfa, Il6, and Col1a in white adipose tissue of the FFD group was significantly higher than that of the ND and PHGG groups, whereas those expressions of the PHGG group were significantly lower than those of the ND and FFD groups ( Supplementary Figure S1I–K ).…”

Section: Resultsmentioning

confidence: 99%

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Partially Hydrolyzed Guar Gum Suppresses the Development of Sarcopenic Obesity

et al. 2022

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Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber derived through controlled enzymatic hydrolysis of guar gum, a highly viscous galactomannan derived from the seeds of Cyamopsis tetragonoloba. Here, we examined the therapeutic potential of dietary supplementation with PHGG against sarcopenic obesity using Db/Db mice. Db/Db mice fed a normal diet alone or a fiber-free diet, or supplemented with a diet containing PHGG (5%), were examined. PHGG increased grip strength and the weight of skeletal muscles. PHGG increased the short-chain fatty acids (SCFAs) concentration in feces and sera. Concerning innate immunity, PHGG decreased the ratio of inflammatory cells, while increasing the ratio of anti-inflammatory cells in the small intestine. The present study demonstrated the preventive effect of PHGG on sarcopenic obesity. Changes in nutrient absorption might be involved through the promotion of an anti-inflammatory shift of innate immunity in the intestine accompanied by an increase in SCFA production by PHGG.

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Section: Resultsmentioning

confidence: 99%

“…Palmitic acid methyl ester was detected in the selective ion monitoring mode. All results were normalized to the peak height of the C17:0 internal standard [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Partially Hydrolyzed Guar Gum Suppresses the Development of Sarcopenic Obesity

et al. 2022

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“…A recent analysis pooled results from a series of prospective cohort studies showed that higher LA intake was associated with a modestly lower risk of mortality from all causes, such as cardiovascular disease and cancer [ 35 ]. Observational data reveals that low circulating DGLA level is associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure [ 36 ], diabetic retinopathy [ 37 ]; while A high serum DGLA level was associated with obesity, body fat accumulation, a high ALT level, and insulin resistance in patients with type 2 diabetes [ 38 ]. However, the TG-lowering effect of other fatty acids is still in the exploratory stage.…”

Section: Discussionmentioning

confidence: 99%

Icosapent ethyl therapy for very high triglyceride levels: a 12-week, multi-center, placebo-controlled, randomized, double-blinded, phase III clinical trial in China

Wang¹,

Zhang²,

Qu³

et al. 2023

Lipids Health Dis

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Objectives Eicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort. Methods Patients having TG levels (5.6–22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362). Results Random assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P < 0.001). In addition, plasma concentration of non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol, and VLDL-TG remarkedly reduced after IPE (4 g/day) treatment by a median of 14.6%, 27.9%, and 25.2%, respectively compared with participants in placebo group. Compared to the placebo, neither 4 nor 2 g of IPE daily elevated LDL-C levels with statistical significance. IPE was well tolerated by all the treatment groups. Conclusions IPE at 4 g/day dramatically lowered other atherogenic lipids without a noticeable increase in LDL-C, thereby decreasing TG levels in an exceptionally high-TG Chinese population.

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“…A propensity score matching-based case–control study shows elevated five n -6 polyunsaturated fatty acids including GLA, which were independent protective factors of DR ( Li et al, 2020 ). The sectional study of the KAMOGAWA-DM cohort study shows low circulating dihomo-gamma-linolenic acid negatively associated with DR ( Okamura et al, 2021 ). ω-3 fatty acids can prevent DR ( Behl and Kotwani 2017 ), and docosahexaenoic acid (DHA) alleviates retinal oxidative stress and inflammation in retinal diseases ( Saenz de Viteri et al, 2020 ; Suzumura et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy

Kong

Sun

et al. 2022

Front. Pharmacol.

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Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug.

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Low circulating dihomo-gamma-linolenic acid is associated with diabetic retinopathy: a cross sectional study of KAMOGAWA-DM cohort study

Cited by 9 publications

References 47 publications

Partially Hydrolyzed Guar Gum Suppresses the Development of Sarcopenic Obesity

Partially Hydrolyzed Guar Gum Suppresses the Development of Sarcopenic Obesity

Icosapent ethyl therapy for very high triglyceride levels: a 12-week, multi-center, placebo-controlled, randomized, double-blinded, phase III clinical trial in China

Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy

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