Pennington Biomedical Research Center System

Baton Rouge, LA, United States

Pennington Biomedical Research Center System

Baton Rouge, LA, United States
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Zhang L.,Pennington Biomedical Research Center System | Zhang L.,Louisiana State University | Dasuri K.,Pennington Biomedical Research Center System | Dasuri K.,Louisiana State University | And 12 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2013

Cerebral amyloid angiopathy (CAA) occurs in nearly every individual with Alzheimer's disease (AD) and Down's syndrome, and is the second largest cause of intracerebral hemorrhage. Mouse models of CAA have demonstrated evidence for increased gliosis contributing to CAA pathology. Nearly two thirds of Americans are overweight or obese, with little known about the effects of obesity on the brain, although increasingly the vasculature appears to be a principle target of obesity effects on the brain. In the current study we describe for the first time whether diet induced obesity (DIO) modulates glial reactivity, amyloid levels, and inflammatory signaling in a mouse model of CAA. In these studies we identify surprisingly that DIO does not significantly increase Aβ levels, astrocyte (GFAP) or microglial (IBA-1) gliosis in the CAA mice. However, within the hippocampal gyri a localized increase in reactive microglia were increased in the CA1 and stratum oriens relative to CAA mice on a control diet. DIO was observed to selectively increase IL-6 in CAA mice, with IL-1β and TNF-α not increased in CAA mice in response to DIO. Taken together, these data show that prolonged DIO has only modest effects towards Aβ in a mouse model of CAA, but appears to elevate some localized microglial reactivity within the hippocampal gyri and selective markers of inflammatory signaling. These data are consistent with the majority of the existing literature in other models of Aβ pathology, which surprisingly show a mixed profile of DIO effects towards pathological processes in mouse models of neurodegenerative disease. The importance for considering the potential impact of ceiling effects in pathology within mouse models of Aβ pathogenesis, and the current experimental limitations for DIO in mice to fully replicate metabolic dysfunction present in human obesity, are discussed. This article is part of a Special Issue entitled: Animal Models of Disease. © 2012.


Freeman L.R.,Pennington Biomedical Research Center System | Zhang L.,Pennington Biomedical Research Center System | Dasuri K.,Pennington Biomedical Research Center System | Fernandez-Kim S.-O.,Pennington Biomedical Research Center System | And 2 more authors.
PLoS ONE | Year: 2012

Mutations in amyloid precursor protein (APP) have been most intensely studied in brain tissue for their link to Alzheimer's disease (AD) pathology. However, APP is highly expressed in a variety of tissues including adipose tissue, where APP is also known to exhibit increased expression in response to obesity. In our current study, we analyzed the effects of mutant APP (E693Q, D694N, K670N/M671L) expression toward multiple aspects of adipose tissue homeostasis. These data reveal significant hypoleptinemia, decreased adiposity, and reduced adipocyte size in response to mutant APP, and this was fully reversed upon high fat diet administration. Additionally, mutant APP was observed to significantly exacerbate insulin resistance, triglyceride elevations, and macrophage infiltration of adipose tissue in response to a high fat diet. Taken together, these data have significant implications for linking mutant APP expression to adipose tissue dysfunction and global changes in endocrine and metabolic function under both obesogenic and non-obesogenic conditions. © 2012 Freeman et al.


PubMed | Pennington Biomedical Research Center System
Type: Journal Article | Journal: PloS one | Year: 2012

Mutations in amyloid precursor protein (APP) have been most intensely studied in brain tissue for their link to Alzheimers disease (AD) pathology. However, APP is highly expressed in a variety of tissues including adipose tissue, where APP is also known to exhibit increased expression in response to obesity. In our current study, we analyzed the effects of mutant APP (E693Q, D694N, K670N/M671L) expression toward multiple aspects of adipose tissue homeostasis. These data reveal significant hypoleptinemia, decreased adiposity, and reduced adipocyte size in response to mutant APP, and this was fully reversed upon high fat diet administration. Additionally, mutant APP was observed to significantly exacerbate insulin resistance, triglyceride elevations, and macrophage infiltration of adipose tissue in response to a high fat diet. Taken together, these data have significant implications for linking mutant APP expression to adipose tissue dysfunction and global changes in endocrine and metabolic function under both obesogenic and non-obesogenic conditions.


PubMed | Pennington Biomedical Research Center System
Type: Journal Article | Journal: Obesity surgery | Year: 2010

Systemic sympathetic stimulation with caffeine and ephedrine increased metabolic rate, reduced food intake, and improved body composition but had systemic adverse events. We hypothesize that selective sympathetic stimulation of the upper gastrointestinal tract will preserve the advantages of systemic sympathetic stimulation without its adverse events. This study evaluated the effect of splanchnic nerve stimulation on metabolic rate, food intake, and body composition.Sixteen Sprague Dawley rats had monopolar electrodes placed on the superior common splanchnic nerve innervating the celiac ganglia. An indifferent electrode was placed subcutaneously on the back. The animals were placed on a 60% fat diet, and eight rats were stimulated for 6 weeks. The stimulation was advanced over 3 days from 0.6 mA to 3 mA. Metabolic rate and food intake were measured daily; weight change was monitored weekly, and body composition was determined by nuclear magnetic resonance (NMR) at the end of the study. Four of the eight animals had metabolic rate measured three times over 2-day periods at 0 mA, 1 mA, and 3 mA of stimulation in a metabolic chamber.Except for the first week of stimulation, there was no difference in body weight between the stimulated and control groups. Cumulative food intake was less in the stimulated group (p<0. 001). The lean-to-fat ratio was greater in the stimulated group (p<0. 01), and the animals that received incremental stimulation showed significantly augmented metabolic rate (p<0. 02).Splanchnic nerve stimulation decreased food intake, increased metabolic rate, and improved body composition.

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