A Role for Astrocytes in the Central Control of Metabolism

Yi, Chun-Xia; Habegger, Kirk M.; Chowen, Julie A.; Stern, Javier E.; Tschöp, Matthias H.

doi:10.1159/000324888

Cited by 52 publications

(49 citation statements)

References 114 publications

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“…However, lipids are normally metabolised by the astrocytes which supply the neurons with ketone bodies particularly during suckling and starvation when lipids are the main energy supply (129) . Thus, these saturated long-chain acyl Co-A may only be present in quantity in astrocytes.…”

Section: Hypothalamic Fatty Acid Metabolismmentioning

confidence: 99%

Hypothalamic dysfunction in obesity

Williams

2012

Proc. Nutr. Soc.

115

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A growing number of studies have shown that a diet high in long chain SFA and/or obesity cause profound changes to the energy balance centres of the hypothalamus which results in the loss of central leptin and insulin sensitivity. Insensitivity to these important anorexigenic messengers of nutritional status perpetuates the development of both obesity and peripheral insulin insensitivity. A high-fat diet induces changes in the hypothalamus that include an increase in markers of oxidative stress, inflammation, endoplasmic reticulum (ER) stress, autophagy defect and changes in the rate of apoptosis and neuronal regeneration. In addition, a number of mechanisms have recently come to light that are important in the hypothalamic control of energy balance, which could play a role in perpetuating the effect of a high-fat diet on hypothalamic dysfunction. These include: reactive oxygen species as an important second messenger, lipid metabolism, autophagy and neuronal and synaptic plasticity. The importance of nutritional activation of the Toll-like receptor 4 and the inhibitor of NF-kB kinase subunit b/NK-kB and c-Jun amino-terminal kinase 1 inflammatory pathways in linking a high-fat diet to obesity and insulin insensitivity via the hypothalamus is now widely recognised. All of the hypothalamic changes induced by a high-fat diet appear to be causally linked and inhibitors of inflammation, ER stress and autophagy defect can prevent or reverse the development of obesity pointing to potential drug targets in the prevention of obesity and metabolic dysfunction.Hypothalamus: Obesity: High-fat diet: Inflammation: Neuronal and synaptic plasticityThe developed world is currently facing an epidemic of obesity. Diseases associated with obesity, particularly type 2 diabetes, CVD, cancer, stroke and mental health issues, including dementia (1,2) are provoking a crisis in health care, adversely affecting health and life expectancy and increasing health care costs, estimated to be up to £45 billion by 2050 in the UK alone (3) . Direct and indirect costs of type 2 diabetes, for example, one of the major health consequences of obesity, are currently £21 . 8 billion and set to rise to £35 . 6 billion by 2035-36 in the UK (4) .Obesity is the result of a disproportionately high energy intake compared to energy expenditure and is a complex interaction between environmental and genetic factors (5) with monogenic defects being relatively rare (6) . It seems obvious that an energy-dense diet, high in saturated fat and sugar, should cause weight gain and increased adiposity; nonetheless it appears that these diets cause a profound change in energy balance that does not result from a simple increase in energetic intake. Diet composition, particularly the presence of long-chain saturated fats, results in metabolic dysfunction and increased adiposity and body weight, Abbreviations: AgRP, agouti-related peptide; ARC, arcuate nuclei; CART, cocaine and amphetamine-regulated transcript; CNTF, ciliary neurotrophic factor; ER, endoplasmic reticulum; I...

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Section: Hypothalamic Fatty Acid Metabolismmentioning

confidence: 99%

Hypothalamic dysfunction in obesity

Williams

2012

Proc. Nutr. Soc.

115

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“…Astrocytes were reported to participate in diverse neuroendocrine processes over 2 decades ago (4,5), although their importance in the control of appetite and energy balance has only recently come to the forefront (6)(7)(8)(9)(10)(11). Astrocytes and tanycytes, the specialized glial cells lining the third ventricle, transport nutrients into and within the brain, express receptors for numerous neuropeptides, neurotransmitters, and growth factors, produce neuroactive substances, and express key enzymes necessary for sensing and processing nutritional signals (2,6,(12)(13)(14)(15), situating them as prime targets for metabolic signals and control.…”

Section: Introductionmentioning

confidence: 99%

Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

Fuente-Martín¹,

García‐Cáceres²,

Granado³

et al. 2012

J. Clin. Invest.

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173

186

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Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity.

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“…Hypothalamic neurons (24) and glia (25)(26)(27)(28)(29) are both able to sense glucose, and the importance of astroglia in central nutrient sensing has been recently emphasized (30). It is unclear if glucose modulation of LCFACoA metabolism occurs in neurons and/or astrocytes and whether or not such a feature distinguishes hypothalamic nuclei from other brain regions.…”

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confidence: 99%

Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes

Taïb

Bouyakdan

Hryhorczuk

et al. 2013

Journal of Biological Chemistry

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Background: Hypothalamic long-chain fatty acids (LCFA) and glucose are critical for energy balance, but it is not known if their metabolism is coupled. Results: Glucose regulates hypothalamic metabolism of palmitate via AMP-activated kinase. Conclusion: Glucose and LCFA metabolism is coupled in a cell-type and LCFA-dependent manner. Significance: This is the first evidence for glucose regulation of LCFA metabolic fate in the hypothalamus.

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A Role for Astrocytes in the Central Control of Metabolism

Cited by 52 publications

References 114 publications

Hypothalamic dysfunction in obesity

Hypothalamic dysfunction in obesity

Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes

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