Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic <i>ob/ob</i> mice

Kozuka, Chisayo; Shimizu-Okabe, Chigusa; Takayama, Chitoshi; Nakano, K.; Morinaga, Hidetaka; Kinjo, Ayano; Fukuda, Kotaro; Kamei, Asuka; Yasuoka, Akihito; Kondo, Takashi; Abe, Keiko; Egashira, Kensuke; Masuzaki, Hiroaki

doi:10.1080/10717544.2017.1279237

Cited by 32 publications

(22 citation statements)

References 47 publications

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“…Therefore, to overcome extremely low bioavailability of γ‐oryzanol with super high lipophilicity, we encapsulated γ‐oryzanol in polymer poly (DL‐lactide‐co‐glycolide) nanoparticles (Nano‐Orz), and evaluated its metabolically beneficial impact in genetically obese diabetic ob / ob mice, the best‐known most severe diabetic model in mice. Consequently, Nano‐Orz markedly ameliorated fuel dysmetabolism shown in ob / ob mice with an unexpected magnitude (approximately 1,000‐fold lower dose) compared with the regular γ‐oryzanol. Surprisingly, such a conspicuous impact was achievable by its administration once every 2 weeks.…”

Section: Approach Toward the Practical Use And Social Implementation mentioning

confidence: 94%

“…Surprisingly, such a conspicuous impact was achievable by its administration once every 2 weeks. Besides the excellent impact on dysfunction of the hypothalamus and pancreatic islets, Nano‐Orz markedly decreased ER stress and inflammation in the liver and adipose tissue.…”

Section: Approach Toward the Practical Use And Social Implementation mentioning

confidence: 98%

“…We showed that Nano‐Orz did decrease the Firmicutes ‐to‐ Bacteroidetes ratio, as well as a trend toward an increase in plasma short chain fatty acids levels in mice. Taken together, nanotechnology‐based developments of functional foods oriented toward γ‐oryzanol might shed light on the novel approach to obesity in humans.…”

Section: Approach Toward the Practical Use And Social Implementation mentioning

confidence: 99%

“…In the brain, the arcuate nucleus in the hypothalamus is one of the main control centers for appetite regulation through input of a variety of hormones and the autonomic nerve system (also known as a regulatory system of metabolic hunger). Noticeably, excessive intake of animal fats provokes microglial inflammation and cellular stresses, such as endoplasmic reticulum (ER) stress and oxidant stress in the hypothalamus, paralyzing the regulatory system of metabolic hunger, thus creating a condition where the brain cannot correctly judge the energy intake appropriate for the body. It is as if the brain is ‘hacked.’ When mice are fed animal fat‐rich foods, activated microglia infiltrates into the hypothalamus within a couple of days.…”

Section: Introductionmentioning

confidence: 99%

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Brown rice‐specific γ‐oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans

Masuzaki

Kozuka

Okamoto

et al. 2018

J of Diabetes Invest

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Chronic overconsumption of animal fats causes a variety of health problems, including diabetes mellitus and obesity. Underlying molecular mechanisms encompass leptin resistance, a decrease in rewarding effects of physical activities, xanthine oxidase-induced oxidative stress in vasculature and peripheral tissue, impaired activation of incretin signaling, deviation in food preference, and dysbiosis of gut microbiota. Based on our clinical observation that daily intake of brown rice effectively ameliorates bodyweight gain, impaired glucose tolerance/insulin resistance and dependence on fatty foods in obese, prediabetes men, a line of research on brown rice (rice bran)-derived γ-oryzanol in mice experiments, cultured cells and human clinical trials is underway in our laboratory. Our works in mice showed that γ-oryzanol, an ester mixture of ferulic acid and several kinds of phytosterols, acts as a molecular chaperone, thereby attenuating the strong preference for animal fats through suppression of endoplasmic reticulum stress in the hypothalamus. In pancreatic islets from both high-fat diet-induced and streptozotocin-induced diabetic mice, γ-oryzanol ameliorates endoplasmic reticulum stress and protects β-cells against apoptosis. Noticeably, γ-oryzanol also acts as a potent inhibitor against deoxyribonucleic acid methyltransferases in the brain reward system (striatum) in mice, thereby attenuating, at least partly, the preference for a high-fat diet through the epigenetic modulation of striatal dopamine D2 receptor. Because dopamine D2 receptor signaling in the brain reward system is considerably attenuated in obese humans and rodents, γ-oryzanol might represent a unique property to ameliorate both hedonic and metabolic dysregulation of feeding behavior, highlighting a promising prophylactic avenue to protect against metabolic derangement.

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Section: Approach Toward the Practical Use And Social Implementation mentioning

confidence: 94%

Section: Approach Toward the Practical Use And Social Implementation mentioning

confidence: 98%

Section: Approach Toward the Practical Use And Social Implementation mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Brown rice‐specific γ‐oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans

Masuzaki

Kozuka

Okamoto

et al. 2018

J of Diabetes Invest

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“…The second problem is that patients may be uncomfortable with injecting themselves daily, and to overcome this challenge scientists have developed a range of long term sustained-release platforms based on polymers such as poly(L-lactide) and poly(lactic-coglycolic acid) (PLGA). These materials have achieved promising results, offering long-lasting sustained release (some function for up to 30-60 days) (Kozuka et al, 2017;Ying et al, 2017;Yu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Insulin-loaded PLGA microspheres for glucose-responsive release

Williams

et al. 2017

Drug Delivery

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Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N-vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 ± 0.15 and 82.6 ± 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes. ARTICLE HISTORY

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Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease

Zhang

Dalan

et al. 2022

Advanced Materials

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Ischemic heart disease (IHD) is the leading cause of disability and mortality worldwide. Reactive oxygen species (ROS) have been shown to play key roles in the progression of diabetes, hypertension, and hypercholesterolemia, which are independent risk factors that lead to atherosclerosis and the development of IHD. Engineered biomaterial‐based nanomedicines are under extensive investigation and exploration, serving as smart and multifunctional nanocarriers for synergistic therapeutic effect. Capitalizing on cell/molecule‐targeting drug delivery, nanomedicines present enhanced specificity and safety with favorable pharmacokinetics and pharmacodynamics. Herein, the roles of ROS in both IHD and its risk factors are discussed, highlighting cardiovascular medications that have antioxidant properties, and summarizing the advantages, properties, and recent achievements of nanomedicines that have ROS scavenging capacity for the treatment of diabetes, hypertension, hypercholesterolemia, atherosclerosis, ischemia/reperfusion, and myocardial infarction. Finally, the current challenges of nanomedicines for ROS‐scavenging treatment of IHD and possible future directions are discussed from a clinical perspective.

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Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice

Cited by 32 publications

References 47 publications

Brown rice‐specific γ‐oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans

Brown rice‐specific γ‐oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans

Insulin-loaded PLGA microspheres for glucose-responsive release

Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease

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