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Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue
- Source :
- Physiological Genomics. 48:420-427
- Publication Year :
- 2016
- Publisher :
- American Physiological Society, 2016.
-
Abstract
- Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin ( Retn) transgene specifically in adipose tissue (SHR- Retn), we have observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles, and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances. In the current study, we have analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR- Retn vs. nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR- Retn transgenic rats compared with SHR controls showed a lower relative weight (0.71 ± 0.05 vs. 0.91 ± 0.08 g/100 g body wt, P < 0.05), significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids (658 ± 50 vs. 856 ± 45 and 864 ± 47 vs. 1,086 ± 35 nmol/g/2 h, P ≤ 0.01, respectively), and significantly decreased palmitate oxidation (37.6 ± 4.5 vs. 57 ± 4.1 nmol/g/2 h, P = 0.007) and glucose oxidation (277 ± 34 vs. 458 ± 38 nmol/g/2 h, P = 0.001). In addition, in vivo microPET imaging revealed significantly reduced 18F-FDG uptake in BAT induced by exposure to cold in SHR- Retn vs. control SHR (232 ± 19 vs. 334 ± 22 kBq/ml, P < 0.05). Gene expression profiles in BAT identified differentially expressed genes involved in skeletal muscle and connective tissue development, inflammation and MAPK and insulin signaling. These results provide evidence that autocrine effects of resistin attenuate differentiation and activity of BAT and thus may play a role in the pathogenesis of insulin resistance in the rat.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Physiology
Transgene
Palmitates
Adipokine
Fatty Acids, Nonesterified
Biology
Mice
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Spontaneously hypertensive rat
Adipose Tissue, Brown
Rats, Inbred SHR
Internal medicine
Brown adipose tissue
Genetics
medicine
Animals
Insulin
Resistin
Obesity
Muscle, Skeletal
Autocrine signalling
Mice, Inbred BALB C
Lipid Metabolism
medicine.disease
Mitochondria
Rats
Autocrine Communication
Glucose
030104 developmental biology
medicine.anatomical_structure
Endocrinology
030220 oncology & carcinogenesis
Insulin Resistance
Rats, Transgenic
Transcriptome
Oxidation-Reduction
Subjects
Details
- ISSN :
- 15312267 and 10948341
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Physiological Genomics
- Accession number :
- edsair.doi.dedup.....3df068d0b70d2c3ff7d9abbc1f24ec93
- Full Text :
- https://doi.org/10.1152/physiolgenomics.00122.2015