TY - JOUR
T1 - Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese Mice
AU - Ren, Guang
AU - Hwang, Patrick Tae Joon
AU - Millican, Reid
AU - Shin, Juhee
AU - Brott, Brigitta C.
AU - Van Groen, Thomas
AU - Powell, Craig M.
AU - Bhatnagar, Sushant
AU - Young, Martin E.
AU - Jun, Ho Wook
AU - Kim, Jeong A.
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/5/4
Y1 - 2022/5/4
N2 - Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation. Therefore, we propose a novel technology of providing exogenous NO to improve the metabolic rate and cognitive function by promoting the development of brown adipose tissue. In the present study, we demonstrate the effects of the peptide amphiphiles-NO-releasing nanomatrix gel (PANO gel) on high-fat diet-induced obesity, insulin resistance, and cognitive functions. Eight-week-old male C57BL/6 mice were subcutaneously injected in the brown fat area with the PANO gel or vehicle (PA gel) every 2 weeks for 12 weeks. The PANO gel-injected mice gained less body weight, improved glucose tolerance, and decreased fasting serum insulin and leptin levels compared with the PA gel-injected mice. Insulin signaling in the muscle, liver, and epididymal white adipose tissue was improved by the PANO gel injection. The PANO gel reduced inflammation, increased lipolysis in the epididymal white adipose tissue, and decreased serum lipids and liver triglycerides. Interestingly, the PANO gel stimulated uncoupled protein 1 gene expression in the brown and beige fat tissues. Furthermore, the PANO gel increased the cerebral blood flow and improved learning and memory abilities. Our results suggest that using the PANO gel to supply exogenous NO is a novel technology to treat metabolic disorders and cognitive dysfunctions.
AB - Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation. Therefore, we propose a novel technology of providing exogenous NO to improve the metabolic rate and cognitive function by promoting the development of brown adipose tissue. In the present study, we demonstrate the effects of the peptide amphiphiles-NO-releasing nanomatrix gel (PANO gel) on high-fat diet-induced obesity, insulin resistance, and cognitive functions. Eight-week-old male C57BL/6 mice were subcutaneously injected in the brown fat area with the PANO gel or vehicle (PA gel) every 2 weeks for 12 weeks. The PANO gel-injected mice gained less body weight, improved glucose tolerance, and decreased fasting serum insulin and leptin levels compared with the PA gel-injected mice. Insulin signaling in the muscle, liver, and epididymal white adipose tissue was improved by the PANO gel injection. The PANO gel reduced inflammation, increased lipolysis in the epididymal white adipose tissue, and decreased serum lipids and liver triglycerides. Interestingly, the PANO gel stimulated uncoupled protein 1 gene expression in the brown and beige fat tissues. Furthermore, the PANO gel increased the cerebral blood flow and improved learning and memory abilities. Our results suggest that using the PANO gel to supply exogenous NO is a novel technology to treat metabolic disorders and cognitive dysfunctions.
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U2 - 10.1021/acsami.1c24113
DO - 10.1021/acsami.1c24113
M3 - Article
C2 - 35467831
AN - SCOPUS:85129296335
SN - 1944-8244
VL - 14
SP - 19104
EP - 19115
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 17
ER -