• mice maintained on a high fat diet and infected with Leishmania major generate more IL-4 and IL-5 producing CD4+ T cells compared to wild-type mice
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• the immune response of mice fed a high fat diet to Leishmania major infection is skewed towards a Th2-type response
• in an adoptive transfer experiment, the proliferation of Tg(TcrLCMV)2Aox CD45.2+ cell in mice fed a high fat diet and receiving then immunized with GP61-80 peptide with CpG is reduced compared to in wild-type mice similarly treated
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• dendrictic cells mount reduced IL-12p40 and TNF-alpha responses to stimulation with zymosan, poly(I:C), LPS, imiquimod, and a combination of anti-CD40 antibodies and CpG compared to wild-type mice but similar to wild-type mice fed a high fat diet
• in mice fed a high fat diet, dendritic cell production of IL-12p40, IL-6 and TNF-alpha after 35 to 40 weeks, but not after 6 to 10 weeks, is severely impaired compared to wild-type cells in response to CpG/anti-CD-40 stimulation
• CD8alpha-, but not CD8alpha+, dendritic cells are defective in their ability to produce IL-12p40
• dendritic cells from mice on a high fat diet are severely impaired in their ability to produce Il-12p40, -12p70, -6, and TNF-alpha compared to dendritic cells from wild-type mice on a high fat diet
• however, CD8alpha+ dendritic cells produce normal amounts of Il-12p70 and -12p40
• mice fed a high fat diet and co-stimulated with CpG or LPS have fewer IL-12p40-producing CD8alpha- dendritic cells (4.6+/-1.1%) than wild-type mice fed a high fat diet (15.3+/-2.4%)
• however, the immune responses of bone marrow derived dendritic cells from mice fed a high fat diet or splenic dendritic cells from mice fed a regular diet are normal
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• mice maintained on a high fat diet and infected with Leishmania major produce more IL-4 and IL-5 producing CD4+ T cells compared to wild-type mice
• the immune response of mice fed a high fat diet to Leishmania major infection is skewed towards a Th2-type response
• mice maintained on a high fat diet or regular chow and infected with Leishmania major exhibit an increased swelling and parasitic burden at the site of infection (footpad)
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• plasma leptin levels are low at both 6 and 18 months
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• mice have increased levels of circulating oxidized lipids compared to wild-type mice
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• mice develop severe cholesterolemia when receiving a high fat diet from 6 to 30 weeks (elevated levels are detected at 6, 15, and 30 weeks)
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• mice consume food slower in a new environment than Tg(GFAP-APOE_i4)#Hol Apoetm1Unc/Apoetm1Unc and wild-type mice
• mice require more time to habituate to a novel environment compared to wild-type mice
• mice are less reluctant than wild-type mice to move into an open area
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• reduced exploratory behavior in an open field test by 12 months although normal earlier
• exploratory behavior remains constant over several days whereas controls show higher initial exploratory behavior which drops off quickly
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• at 14 to 17 months of age, mice perform better than Tg(GFAP-APOE_i4)#Hol Apoetm1Unc/Apoetm1Unc and wild-type mice in a rotating holeboard test
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• increased water intake at 18 months
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• increased food intake at 12 and 18 months but not earlier
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• at 6 months as measured in an elevated plus maze
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• mice spend more time than Tg(GFAP-APOE_i4)#Hol Apoetm1Unc/Apoetm1Unc in the center of an open field
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• 41% increase in foot withdrawal latency from painful thermal stimuli
• 100% slower tail withdrawal latency
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• after-discharge duration is significantly prolonged by the sixth trial
• delayed rekindling after 3-4 weeks
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• mice maintained on a high fat diet and infected with Leishmania major generate more IL-4 and IL-5 producing CD4+ T cells compared to wild-type mice
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• after-discharge duration is significantly prolonged by the sixth trial
• delayed rekindling after 3-4 weeks
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• restraint stress at 6 months results in disproportionately low ACTH levels as compared to plasma corticosterone levels
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• very little Schwann cell cytoplasm
• blurring of lipid membrane border between axons and Schwann cells
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• synaptophysin levels are somewhat more reduced than in controls after entorhinal cortex lesion
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• cross-section of unmyelinated axons is irregular
• very little Schwann cell cytoplasm
• blurring of lipid membrane border between axons and Schwann cells
• reduced number of unmyelinated axons
• ratio of unmyelinated to myelinated axons is reduced
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• increased lipid droplets seen at six months
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• increased lipid droplets seen at six months
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• fter 10 min of restraint stress plasma levels are elevated at six months but not at three months
• elevated adrenal levels at six months but not earlier
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• restraint stress at 6 months results in disproportionately low ACTH levels as compared to plasma corticosterone levels
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• decreased interscapular brown fat at 18 but not at 6 months
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• epididymal white fat reduced at both 6 and 18 months
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• cellular composition of lesions is similar among Serpine1-deficient or transgenic, Apoe-deficient genotypes, or Apoe-deficient only mice; at early time points, a greater foam cell content is observed, with more prominent cholesterol clefts and necrotic areas evident with increasing age
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