Regional astrogliosis in the mouse hypothalamus in response to obesity

Abstract

Obesity is associated with chronic low-grade inflammation in peripheral tissues, which contributes to the development of comorbidities such as insulin resistance and cardiovascular disease. While less extensively characterized, obesity also promotes inflammation in the central nervous system (CNS) and the consequences of this inflammation for CNS function are only beginning to be examined. In response to CNS insults such as inflammation, astrocytes undergo a process of hypertrophy and hyperplasia known as reactive astrogliosis. We used immunohistochemistry to examine the differential distribution of the astrocyte marker glial-fibrillary acidic protein (GFAP) in the brains of diet-induced or genetically obese mice compared with their respective lean controls to determine whether different nuclei of the hypothalamus showed comparable astrogliosis in response to obesity. The areas that showed the highest differential GFAP immunoreactivity between lean and obese animals include the medial preoptic, paraventricular, and dorsomedial nuclei. Comparatively, little astrogliosis was seen in the ventromedial nucleus, lateral hypothalamus, or anterior hypothalamic area. In obese animals high levels of GFAP immunoreactivity were often associated with the microvasculature. There were no differences in the differential distribution of GFAP staining between obese animals and their lean controls in the diet-induced compared with the genetic model of obesity. The exact cause(s) of the astrogliosis in obesity is not known. The finding that obesity causes a distinct pattern of elevated GFAP immunoreactivity associated with microvessels suggests that the astrogliosis may be occurring as a response to changes at the blood–brain barrier and/or in the peripheral circulation.

Obesity induces neuroinflammation mediated by altered expression of the renin–angiotensin system in mouse forebrain nuclei

“…Our findings that HFD consumption leads to increases in the number and size of the cell bodies of Iba-1-positive microglia, as well as increases in gene expression and staining for the astrocytic marker, GFAP, within the ARC are consistent with these previously-published studies. Furthermore, there is also evidence that GFAP immunoreactivity becomes elevated within the other specific nuclei of the hypothalamus, including the PVN of genetically and diet-induced obese female mice [38], which is consistent with our findings that GFAP mRNA and immunoreactivity are also elevated within the PVN.…”

“…Previous studies have ascertained that the level of GFAP, which is largely expressed in astrocytes, is increased in specific brain regions in response to various threats to the internal milieu of the brain [13, 37, 38]. Figures 4 and 5 depict the extent to which maintenance on a HFD for 8 wks impacts immunostaining for this astrocytic marker within the SFO, ARC, PaPVN, PeVN, PVN, and DMH.…”

“…Astrocytes are capable of sensing and responding to hypertensive and obesigenic stimuli [13, 37, 38]. They become activated during obesity [13, 38] and can then impact neuronal signaling within forebrain autonomic control centers through a variety of mechanisms [51].…”

Vitamin C Deficiency in the Brain Impairs Cognition, Increases Amyloid Accumulation and Deposition, and Oxidative Stress in APP/PSEN1 and Normally Aging Mice

“…GFAP was detected using previously described methods 70 . Incubation with primary antibody - 1:1,000 anti-GFAP (Cat.#MAB360, Millipore, Bedford, MA) diluted in blocking buffer (5% milk, TBS-0.1% Tween 20), occurred overnight at 4°C with shaking.…”

Chronic Low-Grade Inflammation in Metabolic Disorders: Relevance for Behavioral Symptoms

“…Relevant to brain functions and behavior, the chronic low-grade inflammatory state that characterizes obesity and related metabolic disorders manifests also in the central nervous system (CNS). In the brain, cytokines are released by glial cells, including astrocytes and microglia, and experimental studies in rodents with diet-induced obesity show an increase in the number of microglial cells with a shift towards a proinflammatory profile [14] together with a recrudescence of activated astrocytes in the CNS [15]. Finally, it was recently shown that peripheral immune cells are also recruited into the CNS in obese rats fed with a high-fat diet [16].…”