Hypothalamic PGC-1α Protects Against High-Fat Diet Exposure by Regulating ERα

Morselli, Eugenia; Fuente-Martín, Esther; Finan, Brian; Kim, Min; Frank, Aaron; García‐Cáceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael D.; Kalainayakan, Sarada Preeta; Li, Dan L.; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F.; Tschöp, Matthias H.; Clegg, Deborah J.

doi:10.1016/j.celrep.2014.09.025

Cited by 167 publications

(175 citation statements)

References 61 publications

(83 reference statements)

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“…The effects of long-chain saturated FAs are seen in both astrocytes and microglia, where they induce the release of inflammatory molecules. In contrast, this inflammation does not occur in response to non-saturated FAs (Milanski et al 2009, Gupta et al 2012, Morselli et al 2014, Valdearcos et al 2014. Thus, the astrocytic signals released to the surrounding neurons depend on the specific type of nutrient perceived by these cells and this in turn most likely affects neuronal metabolic sensing.…”

Section: R62mentioning

confidence: 95%

“…Moreover, females may be more resistant than males to obesityassociated secondary effects due, at least in part, to the higher expression of ERα in astrocytes (Morselli et al 2014). Thus, the sex differences observed in these cells could possibly participate in the sexually dimorphic inflammatory response to HFDs (Louwe et al 2012, Morselli et al 2014.…”

Section: Sex Differences In the Astroglial Response To Fasmentioning

confidence: 99%

“…This possibility is suggested by the fact that glial cells present sexually dimorphic characteristics and responses, with these differences being at least partially due to the influence of sex steroids (Chowen et al 1995, Melcangi et al 2001, Acaz-Fonseca et al 2016. Indeed, astrocytes express receptors for estrogens, androgens and progesterone (Pfaff & Keiner 1973, Garcia-Segura et al 1996b, Melcangi et al 2001, Garcia-Ovejero et al 2005 and sex steroids are reported to modulate the glial response to HFD (Louwe et al 2012, Morselli et al 2014. Sex steroids exert neuroprotective effects in various brain regions, with glial cells participating in this phenomenon (Azcoitia et al 2003, Garcia-Ovejero et al 2005, Barreto et al 2009, Ghorbanpoor et al 2014); thus, it is possible that sex hormones could protect against the deleterious effects of HFD-induced obesity on hypothalamic metabolic neuronal circuits by actions on the neighboring glia.…”

Section: Introductionmentioning

confidence: 99%

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Glial cells and energy balance

Argente-Arizón

Guerra-Cantera

Garcia-Segura

et al. 2017

Journal of Molecular Endocrinology

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The search for new strategies and drugs to abate the current obesity epidemic has led to the intensification of research aimed at understanding the neuroendocrine control of appetite and energy expenditure. This intensified investigation of metabolic control has also included the study of how glial cells participate in this process. Glia, the most abundant cell type in the central nervous system, perform a wide spectrum of functions and are vital for the correct functioning of neurons and neuronal circuits. Current evidence indicates that hypothalamic glia, in particular astrocytes, tanycytes and microglia, are involved in both physiological and pathophysiological mechanisms of appetite and metabolic control, at least in part by regulating the signals reaching metabolic neuronal circuits. Glia transport nutrients, hormones and neurotransmitters; they secrete growth factors, hormones, cytokines and gliotransmitters and are a source of neuroprogenitor cells. These functions are regulated, as glia also respond to numerous hormones and nutrients, with the lack of specific hormonal signaling in hypothalamic astrocytes disrupting metabolic homeostasis. Here, we review some of the more recent advances in the role of glial cells in metabolic control, with a special emphasis on the differences between glial cell responses in males and females.

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Section: R62mentioning

confidence: 95%

Section: Sex Differences In the Astroglial Response To Fasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glial cells and energy balance

Argente-Arizón

Guerra-Cantera

Garcia-Segura

et al. 2017

Journal of Molecular Endocrinology

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“…Activation of inflammatory microglia may contribute to the loss of synapses on hippocampal dentate granule neuron dendrites caused by obesity and diabetes (Stranahan et al, 2008b; Hao et al, 2016). The ability of neurons to respond adaptively to bioenergetic and oxidative stress is compromised by excessive energy intake as indicated by reduced expression of BDNF (Stranahan et al, 2008b), PGC-1α (Morselli et al, 2014), and SIRT1 (Heyward et al, 2016). Obese and diabetic rodents exhibit elevated glucocorticoid levels, which can suppress BDNF expression and impair hippocampal synaptic plasticity and neurogenesis (Stranahan et al, 2008a; Wosiski-Kuhn et al, 2014).…”

Section: Metabolic Factors Can Accelerate or Decelerate Brain Agingmentioning

confidence: 99%

Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States

2018

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During aging, the cellular milieu of the brain exhibits tell-tale signs of compromised bioenergetics, impaired adaptive neuroplasticity and resilience, aberrant neuronal network activity, dysregulation of neuronal Ca2+ homeostasis, the accrual of oxidatively modified molecules and organelles, and inflammation. These alterations render the aging brain vulnerable to Alzheimer’s and Parkinson’s diseases and stroke. Emerging findings are revealing mechanisms by which sedentary overindulgent lifestyles accelerate brain aging, whereas lifestyles that include intermittent bioenergetic challenges (exercise, fasting, and intellectual challenges) foster healthy brain aging. Here we provide an overview of the cellular and molecular biology of brain aging, how those processes interface with disease-specific neurodegenerative pathways, and how metabolic states influence brain health.

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“…These findings can further be described by the fact that storage of fat beyond that required for immediate energy expenditure may represent an evolutionary pressure discouraging high fat intake in men. Following consumption of a high fat diet, the brain tissue of males mirrored the fatty acid composition of the diet whereas in females, this did not occur (Morselli et al, 2014). The males had elevated levels of saturated fatty acids such as palmitic acid as well as elevations in sphingolipids and ceramides which were associated with elevated markers of inflammation when compared to female mice.…”

Section: Teleological Explanation For Sex Differences In Adipose Tmentioning

confidence: 99%

The sexual dimorphism of obesity

Palmer

Clegg

2015

Molecular and Cellular Endocrinology

674

537

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The NIH has recently highlighted the importance of sexual dimorphisms and has mandated inclusion of both sexes in clinical trials and basic research. In this review we highlight new and novel ways sex hormones influence body adiposity and the metabolic syndrome. Understanding how and why metabolic processes differ by sex will enable clinicians to target and personalize therapies based on gender. Adipose tissue function and deposition differ by sex. Females differ with respect to distribution of adipose tissues, males tend to accrue more visceral fat, leading to the classic android body shape which has been highly correlated to increased cardiovascular risk; whereas females accrue more fat in the subcutaneous depot prior to menopause, a feature which affords protection from the negative consequences associated with obesity and the metabolic syndrome. After menopause, fat deposition and accrual shift to favor the visceral depot. This shift is accompanied by a parallel increase in metabolic risk reminiscent to that seen in men. A full understanding of the physiology behind why, and by what mechanisms, adipose tissues accumulate in specific depots and how these depots differ metabolically by sex is important in efforts of prevention of obesity and chronic disease. Estrogens, directly or through activation of their receptors on adipocytes and in adipose tissues, facilitate adipose tissue deposition and function. Evidence suggests that estrogens augment the sympathetic tone differentially to the adipose tissue depots favoring lipid accumulation in the subcutaneous depot in women and visceral fat deposition in men. At the level of adipocyte function, estrogens and their receptors influence the expandability of fat cells enhancing the expandability in the subcutaneous depot and inhibiting it in the visceral depot. Sex hormones clearly influence adipose tissue function and deposition, determining how to capture and utilize their function in a time of caloric surfeit, requires more information. The key will be harnessing the beneficial effects of sex hormones in such a way as to provide ‘healthy’ adiposity.

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Hypothalamic PGC-1α Protects Against High-Fat Diet Exposure by Regulating ERα

Cited by 167 publications

References 61 publications

Glial cells and energy balance

Glial cells and energy balance

Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States

The sexual dimorphism of obesity

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