Modulation of adipocyte size and fat pad weight via resveratrol releasing scaffolds implanted into the epididymal adipose tissue

Abstract

Lipid overload of the adipose tissue, which can be caused by overnutrition, underlies metabolic disease. We hypothesized that increasing the energy demand of adipose tissue is a promising strategy to combat excessive lipid accumulation. Resveratrol, a natural polyphenol, activates lipid catabolism in fat tissue; however, its clinical success is hindered by poor bioavailability. Here, we implanted resveratrol releasing poly(lactide‐co‐glycolide) scaffolds into epididymal fat to overcome its poor bioavailability with the goal of enhancing local lipid catabolism. In lean mice, resveratrol scaffolds decreased adipocyte size relative to scaffolds with no drug, a response that correlated with AMP kinase activation. Immunohistochemistry indicated that macrophages and multinucleated giant cells within the scaffold expressed carnitine palmitoyltransferase 1 (CPT1) at higher levels than other cells in the adipose tissue. Furthermore, resveratrol increased CPT1 levels in cultured macrophages. Taken together, we propose that resveratrol scaffolds decrease adipocyte size because resveratrol increases lipid utilization in scaffold‐infiltrating immune cells, possibly through elevating CPT1 levels or activity. In a follow‐up study, mice that received resveratrol scaffolds 28‐day prior to a high‐fat diet exhibited decreased weight gain, adipose tissue expansion, and adipocyte hypertrophy compared to mice with control scaffolds. Notably, this scaffold‐based strategy required a single resveratrol administration compared to the daily regiment generally needed for oral administration. These results indicate that localized delivery of metabolism modulating agents to the adipose tissue may overcome issues with bioavailability and that the role of biomaterials should be further investigated in this therapeutic strategy for metabolic disease.

Using polyphenols as a relevant therapy to diabetes and its complications, a review

“…Aires et al ( 2017) studied the effects of resveratrol on CPT deficient fibroblasts and found that it was capable of modulating the expression of several microRNAs related to CPT and other enzymes related with energy metabolism such as adenosine monophosphate-activated protein kinase (AMPK). The increased expression/activity of CPT was also verified by Bastin, Lopes-Costa, and Djouadi (2011) in CPT deficient patients through an increase in the amount of CPT enzyme and its expression and fatty acid oxidation, by Murphy et al (2020) who studied the effects on implanting a resveratrol releasing scaffold on adipose tissue of mice and by K€ uhn et al (2018). Although resveratrol increased AMPK amounts/activity, this is not the only mechanism through which CPT activity and levels are restored, since using AMPK activators alone did not restore CPT to normal levels in the patients studied by Bastin, Lopes-Costa, and Djouadi (2011).…”

“…Ochiai et al (2004) were only able to find a statistically significant difference in the levels of homocysteine but not in total cholesterol, HDL or LDL, while Kozuma et al (2005) found a statistically significant difference in total cholesterol but not HDL or LDL when compared to the start of their study. There are several studies on the effects of resveratrol on CPT (Aires et al 2017;Bastin, Lopes-Costa, and Djouadi 2011;Murphy et al 2020;K€ uhn et al 2018). Aires et al ( 2017) studied the effects of resveratrol on CPT deficient fibroblasts and found that it was capable of modulating the expression of several microRNAs related to CPT and other enzymes related with energy metabolism such as adenosine monophosphate-activated protein kinase (AMPK).…”

Modern opportunities and prospects for preserving woman’s health

“…Крізь призму жіночого здоров'я, у контексті медикаментозної корекції ожиріння та його ускладнень ресвератрол є потенційно важливим нутрієнтом з доведеною ефективністю. Препарат має доведені антиліпогенні властивості, діє на преадипоцити (індукція апоптозу, пригнічення їхньої проліферації та диференціювання, активація бурої жирової тканини) [44,45].…”

Impact of bioactive molecule inclusion in lyophilized silk scaffolds varies betweenin vivoandin vitroassessments

“…The infiltration of proinflammatory immune cells is associated with an increased production of proinflammatory cytokines including tumor necrosis factor α, IL-1β and IL-6. [54][55][56][57] As a result, biomaterial researchers need to identify the extent of adipose tissue deposition within, and around degrading biomaterials for specific applications [57][58][59][60] and the role this adipose tissue plays in final tissue or organ function.…”