Hypothalamic Damage Is Associated With Inflammatory Markers and Worse Cognitive Performance in Obese Subjects

Puig, Josep; Blasco, Gerard; Daunis‐i‐Estadella, Pepus; Molina, Xavier; Xifra, Gemma; Ricart, Wifredo; Pedraza, Salvador; Fernández‐Aranda, Fernando; Fernández-Real, José Manuel

doi:10.1210/jc.2014-2682

Cited by 52 publications

(47 citation statements)

References 22 publications

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“…This inflammation then causes synaptic remodeling and degeneration in hypothalamus, thereby affecting any regions to which the hypothalamus projects, including brain regions important in cognition (Miller and Spencer, 2014). Additionally, greater hypothalamic damage was associated with higher levels of inflammatory cytokines and worse cognitive performance in obese subjects (Puig et al, 2015). …”

Section: Mechanisms Underlying Sex Differences In Obesity and Alzhmentioning

confidence: 99%

Obesity and sex interact in the regulation of Alzheimer's disease

Moser

Pike

2016

Neuroscience & Biobehavioral Reviews

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, for which a number of genetic, environmental, and lifestyle risk factors have been identified. A significant modifiable risk factor is obesity in mid-life. Interestingly, both obesity and AD exhibit sex differences and are regulated by sex steroid hormones. Accumulating evidence suggests interactions between obesity and sex in regulation of AD risk, although the pathways underlying this relationship are unclear. Inflammation and the E4 allele of apolipoprotein E have been identified as independent risk factors for AD and both interact with obesity and sex steroid hormones. We review the individual and cooperative effects of obesity and sex on development of AD and examine the potential contributions of apolipoprotein E, inflammation, and their interactions to this relationship.

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Section: Mechanisms Underlying Sex Differences In Obesity and Alzhmentioning

confidence: 99%

Obesity and sex interact in the regulation of Alzheimer's disease

Moser

Pike

2016

Neuroscience & Biobehavioral Reviews

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“…Moreover, obese patients appear to have reduced integrity of vital brain circuits, correlating with levels of peripheral inflammation and cognitive dysfunction. These findings suggest that an anatomical mechanism may link increased adiposity with CNS impairment [104, 105]. …”

Section: Gliosis and Obesity In Humansmentioning

confidence: 99%

Glia: silent partners in energy homeostasis and obesity pathogenesis

2016

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Body weight stability requires homeostatic regulation to balance energy intake and energy expenditure. Research on this system and how it is affected by obesity has largely focussed on the role of hypothalamic neurons as integrators of information about long-term fuel storage, short-term nutrient availability and metabolic demand. Recent studies have uncovered glial cells as additional contributors to energy balance regulation and obesity pathogenesis. Beginning with early work on leptin signalling in astrocytes, this area of research rapidly emerged after the discovery of hypothalamic inflammation and gliosis in obese rodents and humans. Current studies have revealed the involvement of a wide variety of glial cell types in the modulation of neuronal activity, regulation of hormone and nutrient availability, and participation in the physiological regulation of feeding behaviour. In addition, one glial type, microglia, has recently been implicated in susceptibility to diet-induced obesity. Together, these exciting new findings deepen our understanding of energy homeostasis regulation and raise the possibility of identifying novel mechanisms that contribute to the pathogenesis of obesity.

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“…A separate MRI study in 44 overweight/obese subjects reported an inverse correlation between systemic inflammation (measured as serum fibrinogen) and the integrity of brain structures involved in food reward and feeding behavior (73). Most recently, diffusion tensor imaging (DTI) was used to screen for hypothalamic damage in 44 obese patients and controls (74••). In the obese cohort, lower axon diffusivity (i.e.…”

Section: Hypothalamic Pathology In Humans?mentioning

confidence: 99%

Hypothalamic inflammation and gliosis in obesity

Dorfman

Thaler

2015

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

120

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Structured Abstract Purpose of review Hypothalamic inflammation and gliosis are recently discovered mechanisms that may contribute to obesity pathogenesis. Current research in this area suggests that investigation of these CNS responses may provide opportunities to develop new weight loss treatments. Recent findings In rodents, hypothalamic inflammation and gliosis occur rapidly with high-fat diet consumption prior to significant weight gain. In addition, sensitivity or resistance to diet-induced obesity in rodents generally correlates with the presence or absence of hypothalamic inflammation and reactive gliosis (brain response to injury). Moreover, functional interventions that increase or decrease inflammation in neurons and glia correspondingly alter diet-associated weight gain. However, some conflicting data have recently emerged that question the contribution of hypothalamic inflammation to obesity pathogenesis. However, several studies have detected gliosis and disrupted connectivity in obese humans, highlighting the potential translational importance of this mechanism. Summary There is growing evidence that obesity is associated with brain inflammation in humans, particularly in the hypothalamus where its presence may disrupt body weight control and glucose homeostasis. More work is needed to determine whether this response is common in human obesity and to what extent it can be manipulated for therapeutic benefit.

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Hypothalamic Damage Is Associated With Inflammatory Markers and Worse Cognitive Performance in Obese Subjects

Cited by 52 publications

References 22 publications

Obesity and sex interact in the regulation of Alzheimer's disease

Obesity and sex interact in the regulation of Alzheimer's disease

Glia: silent partners in energy homeostasis and obesity pathogenesis

Hypothalamic inflammation and gliosis in obesity

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