White adipocyte-targeted dual gene silencing of FABP4/5 for anti-obesity, anti-inflammation and reversal of insulin resistance: Efficacy and comparison of administration routes

Chung, Jee Young; Hong, Juhyeong; Kim, Hyung Jin; Song, Yoonsung; Yong, Seok Beom; Lee, Jieun; Kim, Yong Hee

doi:10.1016/j.biomaterials.2021.121209

Cited by 18 publications

(13 citation statements)

References 44 publications

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“…Fabp4 bind long-chain FFA and are specifically expressed in adipocyte ( Thompson et al, 2018 ). Although the underlying molecular mechanisms of Fabp4 expression and activity have not been fully elucidated, Omega-3 fatty acids were reported to decrease the expression and consecutive secretion of Fabp4, which had a positive effect on anti-obesity and reversal of insulin resistance ( Furuhashi et al, 2016 ; Chung et al, 2021 ). Based on above, we supposed that the Fads1/PPARδ/Fabp4 signaling axis might be a direct target pathway of TF3 to reduce lipid accumulation, providing a more theoretical basis for further drug development and clinical application.…”

Section: Discussionmentioning

confidence: 99%

Effect of theaflavin-3,3′-digallate on leptin-deficient induced nonalcoholic fatty liver disease might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota

Zhou

Zhang²,

Lin³

et al. 2022

Front. Pharmacol.

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Nonalcoholic fatty liver disease (NAFLD), one of the risk factors for hepatitis, cirrhosis, and even hepatic carcinoma, has been a global public health problem. The polyphenol compound theaflavin-3,3′-digallate (TF3), mainly extracted from black tea, has been reported to produce an effect on hypoglycemic and antilipid deposition in vitro. In our study, we further investigated the function and novel mechanisms of TF3 in protecting NAFLD in vivo. By using leptin-deficient obese (ob/ob) mice with NAFLD symptoms, TF3 treatment prevented body weight and waistline gain, reduced lipid accumulation, and alleviated liver function injury, as well as decreased serum lipid levels and TG levels in livers in ob/ob mice, observing no side effects. Furthermore, the transcriptome sequencing of liver tissue showed that TF3 treatment corrected the expression profiles of livers in ob/ob mice compared with that of the model group. It is interesting to note that TF3 might regulate lipid metabolism via the Fads1/PPARδ/Fabp4 axis. In addition, 16S rRNA sequencing demonstrated that TF3 increased the abundance of Prevotellaceae_UCG-001, norank_f_Ruminococcaceae, and GCA-900066575 and significantly decreased that of Parvibacter. Taken together, the effect of TF3 on NAFLD might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota. TF3 might be a promising candidate for NAFLD therapy.

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Section: Discussionmentioning

confidence: 99%

Effect of theaflavin-3,3′-digallate on leptin-deficient induced nonalcoholic fatty liver disease might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota

Zhou

Zhang²,

Lin³

et al. 2022

Front. Pharmacol.

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“…In addition to studying the expression of lipid droplet peripherin-related genes, we also explored the expression of epididymal lipolysis-related genes ( Figure 4 A) and lipid synthesis-related genes ( Figure 4 B) during weight loss, and the expression of epididymal lipid synthesis-related genes ( Figure 4 C) during weight regain. Fatty acid binding protein 4 (FABP4) is an adipokine that coordinates lipid transport in mature adipocyte, and its inhibition in obesity models shows weight loss and normalized insulin response [ 17 ]. Lipoprotein lipase (LPL) belongs to the lipase superfamily, and its main function is to provide tissue-utilized non-esterified fatty acids (NEFA) by breaking down triglycerides (TGs) in lipoprotein particles, such as chylomicrons (CM), very low-density lipoproteins (VLDL), and 2-monoacylglycerol, to provide energy [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

A Comparative Study of the Anti-Obesity Effects of Dietary Sea Cucumber Saponins and Energy Restriction in Response to Weight Loss and Weight Regain in Mice

Wen

Zhao

et al. 2022

Marine Drugs

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Dietary supplementation of sea cucumber saponins and calorie restriction have been proved to be effective in alleviating obesity, but the differences of anti-obesity effects between sea cucumber saponins and energy restriction during weight loss and weight regain are still unknown. In the present study, high-fat-induced obesity mice were randomly divided into three groups, including a high-fat diet group (HF), an energy restriction by 40% group (HF-L), and a sea cucumber saponins group (HF-S), to compare the effects of dietary sea cucumber saponins and energy restriction on the weight, glucose, and lipid metabolism of obese mice during weight loss and weight regain. The results showed that dietary 0.06% sea cucumber saponins and limiting energy intake by 40% had the same weight loss effect. Interestingly, sea cucumber saponins could alleviate impaired glucose tolerance and insulin resistance caused by obesity. In addition, the inhibited SREBP-1c mediated lipogenesis might lead to the alleviation of weight regain after resuming the high-fat diet even when sea cucumber saponins were no longer supplemented. In contrast, limiting energy intake tended to promote lipid synthesis in the liver and white adipose tissue after restoring a high-fat diet, and inflammation was also induced. The findings indicated that sea cucumber saponins could replace calorie restriction to prevent obesity and might be used as a functional food or drug to resist obesity and related diseases caused by obesity.

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“…The NP complex was synthesized using electrostatic complexation following a similar approach previously reported [ 32 , 38 , 39 , 40 ]. Five hundred (500) µL of 10 mg/mL ATS9R solution was added drop-wise to 500 µL of a 10 mg/mL ASO solution under vigorous stirring.…”

Section: Methodsmentioning

confidence: 99%

Divergence of Chemerin Reduction by an ATS9R Nanoparticle Targeting Adipose Tissue In Vitro vs. In Vivo in the Rat

et al. 2022

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Nanoparticles (NPs) can enable delivery of a drug to a targeted tissue. Previous studies have shown that an NP utilizing an adipose targeting sequence (ATS) peptide in conjunction with a drug can selectively deliver the drug to mouse adipose tissues, using the prohibitin protein expressed in adipose tissue as the target of the ATS. Adipose tissue is a major source of the adipokine chemerin, a prohypertensive protein. Liver-derived chemerin, the largest source of circulating chemerin, is biologically inactive in blood pressure regulation. Our goal is to understand if chemerin produced in adipose tissue contributes to blood pressure/hypertension. We hypothesize the ATS drug delivery system could be used specifically to reduce the levels of adipose tissue-derived chemerin. We created an NP consisting of an antisense oligonucleotide (ASO) against chemerin and a FITC-labeled ATS with a nine arginine sequence (ATS9R). In vitro studies showed that the ASO is functional when incorporated into an NP with ATS9R as it reduced chemerin mRNA expression in isolated epidydimal (Epi) and retroperitoneal (RP) fat adipocytes from Dahl SS rats. This same NP reduced chemerin in isolated whole fats. However, this NP was unable to selectively deliver the ASO to adipose tissue in vivo; liver delivery was dominant. Varying NP doses, administration route, and the concentration of components constituting the NP showed no improvement in ASO delivery to fats vs. the liver. Further studies are therefore needed to develop the ATS9R system to deliver an ASO to adipose beds in rats.

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White adipocyte-targeted dual gene silencing of FABP4/5 for anti-obesity, anti-inflammation and reversal of insulin resistance: Efficacy and comparison of administration routes

Cited by 18 publications

References 44 publications

Effect of theaflavin-3,3′-digallate on leptin-deficient induced nonalcoholic fatty liver disease might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota

Effect of theaflavin-3,3′-digallate on leptin-deficient induced nonalcoholic fatty liver disease might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota

A Comparative Study of the Anti-Obesity Effects of Dietary Sea Cucumber Saponins and Energy Restriction in Response to Weight Loss and Weight Regain in Mice

Divergence of Chemerin Reduction by an ATS9R Nanoparticle Targeting Adipose Tissue In Vitro vs. In Vivo in the Rat

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