Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice.
Our previous works demonstrated that brown rice-specific bioactive substance, γ-oryzanol acts as a chaperone, attenuates exaggerated endoplasmic reticulum (ER) stress in brain hypothalamus and pancreatic islets, thereby ameliorating metabolic derangement in high fat diet (HFD)-induced obese diabetic mice. However, extremely low absorption efficiency from intestine of γ-oryzanol is a tough obstacle for the clinical application. Therefore, in this study, to overcome extremely low bioavailability of γ-oryzanol with super-high lipophilicity, we encapsulated γ-oryzanol in polymer poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Nano-Orz), and evaluated its metabolically beneficial impact in genetically obese-diabetic ob/ob mice, the best-known severest diabetic model in mice. To our surprise, Nano-Orz markedly ameliorated fuel metabolism with an unexpected magnitude (∼1000-fold lower dose) compared with regular γ-oryzanol. Furthermore, such a conspicuous impact was achievable by its administration once every 2 weeks. Besides the excellent impact on dysfunction of hypothalamus and pancreatic islets, Nano-Orz markedly decreased ER stress and inflammation in liver and adipose tissue. Collectively, nanotechnology-based developments of functional foods oriented toward γ-oryzanol shed light on the novel approach for the treatment of a variety of metabolic diseases in humans.
a Division of Endocrinology , Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine and.
Chisayo
C
Kozuka
b Department of Molecular Anatomy , Graduate School of Medicine, University of the Ryukyus , Okinawa , Japan.
Chigusa
C
Shimizu-Okabe
b Department of Molecular Anatomy , Graduate School of Medicine, University of the Ryukyus , Okinawa , Japan.
Chitoshi
C
Takayama
c Department of Cardiovascular Medicine and.|d Department of Cardiovascular Research , Development, and Translational Medicine, Kyushu University Graduate School of Medical Sciences , Fukuoka , Japan.
Kaku
K
Nakano
e SENTAN Pharma Inc. , Fukuoka , Japan.
Hidetaka
H
Morinaga
e SENTAN Pharma Inc. , Fukuoka , Japan.
Ayano
A
Kinjo
e SENTAN Pharma Inc. , Fukuoka , Japan.
Kotaro
K
Fukuda
f Kanagawa Academy of Science and Technology , Kanagawa , Japan , and.
Asuka
A
Kamei
f Kanagawa Academy of Science and Technology , Kanagawa , Japan , and.
Akihito
A
Yasuoka
f Kanagawa Academy of Science and Technology , Kanagawa , Japan , and.
Takashi
T
Kondo
f Kanagawa Academy of Science and Technology , Kanagawa , Japan , and.|g Department of Applied Biological Chemistry , Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo , Japan.
Keiko
K
Abe
c Department of Cardiovascular Medicine and.|d Department of Cardiovascular Research , Development, and Translational Medicine, Kyushu University Graduate School of Medical Sciences , Fukuoka , Japan.|e SENTAN Pharma Inc. , Fukuoka , Japan.
Kensuke
K
Egashira
a Division of Endocrinology , Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine and.
Hiroaki
H
Masuzaki
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004337:Drug Carriers; D004339:Drug Compounding; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005518:Food Preferences / Q000187:drug effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007333:Insulin Resistance; D007408:Intestinal Absorption; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008820:Mice, Obese; D050997:Nanomedicine; D053758:Nanoparticles; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D010666:Phenylpropionates / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D008055:Lipids; D010666:Phenylpropionates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C013172:gamma-oryzanol
Type 2 diabetes mellitus; brown rice; nanotechnology; obesity; poly (DL-lactide-co-glycolide); therapeutic modality; γ-oryzanol