The host response to poly(lactide-co-glycolide) scaffolds protects mice from diet induced obesity and glucose intolerance

Autor: Heather L. Struckman, Christopher Isely, Kendall P. Murphy, R. Michael Gower, Michael A. Hendley, Prakasam Annamalai
Rok vydání: 2019
Předmět:
Blood Glucose
Male
medicine.medical_specialty
medicine.medical_treatment
Glucose uptake
Biophysics
Adipokine
Adipose tissue
Bioengineering
02 engineering and technology
Diet
High-Fat
Article
Biomaterials
Impaired glucose tolerance
03 medical and health sciences
Implants
Experimental
Polylactic Acid-Polyglycolic Acid Copolymer
Internal medicine
Diabetes mellitus
Glucose Intolerance
medicine
Animals
Obesity
Insulin-Like Growth Factor I
Adiposity
030304 developmental biology
Epididymis
Glucose Transporter Type 1
0303 health sciences
Tissue Scaffolds
Chemistry
Macrophages
Growth factor
Glucose transporter
Fasting
Organ Size
021001 nanoscience & nanotechnology
medicine.disease
Mice
Inbred C57BL
Endocrinology
Adipose Tissue
Mechanics of Materials
Body Composition
Ceramics and Composites
0210 nano-technology
Wound healing
Proto-Oncogene Proteins c-akt
Zdroj: Biomaterials
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2019.119281
Popis: Underlying metabolic disease is poor adipose tissue function characterized by impaired glucose tolerance and low expression of health promoting adipokines. Currently, no treatments specifically target the adipose tissue and we are investigating polymer scaffolds for localized drug delivery as a therapeutic platform. In this work we implanted porous poly(lactide-co-glycolide) scaffolds into the epididymal fat of mice. Surprisingly, "empty" scaffolds decreased blood glucose levels in healthy mice as well as epididymal fat pad size. By injecting a fluorescent glucose tracer into mice, we determined that glucose uptake increases by 60% in epididymal fat pads with scaffolds; in contrast, glucose uptake was not elevated in other major metabolic organs, suggesting the enhanced glucose uptake at the scaffold implant site was responsible for decreased blood glucose levels. Histology indicated increased cellularity and tissue remodeling around the scaffold and we found increased expression of glucose transporter 1 and insulin-like growth factor 1, which are proteins involved in wound healing that can also modulate blood glucose levels through their promotion of glucose uptake. Regarding clinical translation, "empty" scaffolds decreased obesity and improved glucose tolerance in mice fed a high fat diet. These findings demonstrate increased cellular activity in the adipose tissue, such as that associated with the host response to biomaterial implant, is beneficial in mice suffering from metabolic complications of over nutrition, possibly because it mitigates the positive energy balance that leads to the obese, diabetic state. More broadly, this work reaffirms that in addition to the local host response typically investigated, biomaterial implant has systemic physiological effects and suggests that there may be implications for therapy.
Databáze: OpenAIRE
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