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Most relevant aRtoloMéóPezeRRadónoRtalúñezaRCíaGuIlaRsbRItenItoet
al.. Autophagy impairment aggravates the inhibitory effects of high glucose on os-
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• GóMez-heRnández a, esCRIbano ó, PeRdoMo l, oteRo yF, GaRCía-GóMez G, FeRnández s et
al.. Implication of insulin receptor A isoform and IRA/IGF-IR hybrid receptors in the
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uIllenaRtoloMeIlaedMaRaRCíaGuIlaRoMezeRnándezenIto
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• G-h a, P l, e ó, b M. [Role of brown and perivascular
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Highlights
CURRENT PROJECTS IN 2013:
• Papel de la formación y función del tejido adiposo marrón sobre la patogénesis
de la obesidad: recuperación de la función termogénica marrón como terapia
antiobesidad. D.G.I.P.N., M.C.INN., SAF2011-22555, 2012 hasta 2014, Lead Re-
searcher: Manuel R. Benito De las Heras
• Estudio de los mecanismos de resistencia a insulina: implicaciones en obesidad,
diabetes y sndrome metabólico (MOIR). C.A.M. S2010/BMD-2423, 2012 hasta
2015, Lead Researcher Grupo Consorciado: Manuel R. Benito De las Heras
MOST RELEVANT RESULTS:
Throughout 2013, we have been able to generate the IGF-1R KO and IGF-1R/IR
DKO. This is the first new generation of BAT-specific KO after BATIRKO in the two
thousands. We have studied the development of BATIGFIRKO under standard diet.
The ratio of brown fat mass/body weight did not change versus control upon a
year development. However, lipid content and cell size increased in KO mice versus
control as revealed by interscapular BAT histology. Western-blot analysis showed a
huge increase of IR, IRS-1 and IRS-2 protein expression versus control, suggesting
a compensatory mechanism by the insulin signaling upon IGFIR deletion. In addi-
tion, UCP-1 expression, the BAT thermogenic marker, was significantly decreased.
However, Hsp-60 protein expression did not change in KO mice suggesting that the
mitochondrial mass remained unchanged. Also, the expression of mitochondrial
CPT-1 remained unchanged, suggesting that fatty acid oxidation capacity by BAT
13
remained invariable. Conversely, the expression of ACC and FAS, lipogenic mark- 20
ers, increased very significantly in KO mice versus controls. These data support the T
OR
accumulation of lipid that turned out in hypertrophic brown adipocytes as observed P
RE
by BAT histology in the KO mice. However, the epigonadal white fat mass remained L
unchanged in the KO mice, with a significant reduction in the inguinal white fat A
NU
mass. These data were confirmed by NMR studies at 1 year-old mice. Energy ex- N
penditure studies showed no significant changes in the KO mice versus controls, A
M /
suggesting that diet-induced non-shivering thermogenesis was unaffected. How- E
D
ever, the cold-induced non-shivering thermogenesis was much affected as revealed ER
by the cold-acclimatation studies performed at 5 0C room temperature. Regarding B
CI
MOIR project, we have developed new ADV carrying insulin receptor isoforms IRA
41
or IRB. Gene therapy studies revealed that IRA, but not IRB, were able to impair or
to revert the diabetic phenotype induced in iLIRKO mice by tamoxifen content diet.
