TY - JOUR AB - Astrocytes are specialised glial cells that integrate distinct inputs arising from neurones, other glial cells and the microcirculation to regulate diverse aspects of brain function. A growing body of emerging evidence supports that astrocytes, similar to neurones, also play active roles in the neuroendocrine control of metabolism by responding to afferent nutritional and hormonal cues and translating these metabolic cues into neuronal inputs. Specifically, insulin action in astrocytes has received special emphasis given its newly discovered regulatory role in brain glucose uptake, which until recently was assumed to be an insulin independent process. We now know that insulin signalling in astrocytes regulates metabolic processes and behavioural responses through coupling brain glucose uptake with nutrient availability to maintain energy balance and systemic glucose homeostasis. Moreover, genetic ablation of the insulin receptor in astrocytes is associated with anxiety- and depressive-like behaviours, confirming that these glial cells are involved in the regulation of cognition and mood via insulin action. Here, we provide a comprehensive review of the most relevant findings that have been made over the course of the last few years linking insulin signalling in astrocytes with the pathogenesis of brain metabolic and neurodegenerative diseases; a still unexplored field, but with a high translational potential for developing therapies. AU - Gonzales García, I. AU - Gruber, T. AU - García-Cáceres, C. C1 - 61633 C2 - 50359 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Insulin action on astrocytes: From energy homeostasis to behaviour. JO - J. Neuroendocrinol. VL - 33 IS - 4 PB - Wiley PY - 2021 SN - 0953-8194 ER - TY - JOUR AB - The intranasal (IN) route enables the delivery of insulin to the central nervous system in the relative absence of systemic uptake and related peripheral side effects. Intranasally administered insulin is assumed to travel along olfactory and adjacent pathways and has been shown to rapidly accumulate in cerebrospinal fluid, indicating efficient transport to the brain. Two decades of studies in healthy humans and patients have demonstrated that IN insulin exerts functional effects on metabolism, such as reductions in food intake and body weight and improvements of glucose homeostasis, as well as cognition, ie, enhancements of memory performance both in healthy individuals and patients with mild cognitive impairment or Alzheimer's disease; these studies moreover indicate a favourable safety profile of the acute and repeated use of IN insulin. Emerging findings suggest that IN insulin also modulates neuroendocrine activity, sleep-related mechanisms, sensory perception and mood. Some, but not all studies point to sex differences in the response to IN insulin that need to be further investigated along with the impact of age. “Brain insulin resistance” is an evolving concept that posits impairments in central nervous insulin signalling as a pathophysiological factor in metabolic and cognitive disorders such as obesity, type 2 diabetes and Alzheimer's disease, and, notably, a target of interventions that rely on IN insulin. Still, the negative outcomes of longer-term IN insulin trials in individuals with obesity or Alzheimer's disease highlight the need for conceptual as well as methodological advances to translate the promising results of proof-of-concept experiments and pilot clinical trials into the successful clinical application of IN insulin. AU - Hallschmid, M. C1 - 61134 C2 - 50057 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Intranasal insulin. JO - J. Neuroendocrinol. VL - 33 IS - 4 PB - Wiley PY - 2021 SN - 0953-8194 ER - TY - JOUR AB - There is growing evidence that obesity is associated with inflammation in the brain, which could contribute to the pathogenesis of obesity. In humans, it is challenging to detect brain inflammation in vivo. Recently, quantitative magnetic resonance imaging (qMRI) has emerged as a tool for characterising pathophysiological processes in the brain with reliable and reproducible measures. Proton density imaging provides quantitative assessment of the brain water content, which is affected in different pathologies, including inflammation. We enrolled 115 normal weight, overweight and obese men and women (body mass index [BMI] range 20.1-39.7 kg m(-2), age range 20-75 years, 60% men) to acquire cerebral water content mapping in vivo using MRI at 3 Tesla. We investigated potential associations between brain water content with anthropometric measures of obesity, body fat distribution and whole-body metabolism. No global changes in water content were associated with obesity. However, higher water content values in the cerebellum, limbic lobe and sub-lobular region were detected in participants with higher BMI, independent of age. More specifically, the dorsal striatum, hypothalamus, thalamus, fornix, anterior limb of the internal capsule and posterior thalamic radiation showed the strongest relationship with BMI, independent of age. In a subgroup with available measurements (n = 50), we identified visceral adipose tissue to be the strongest tested link between higher water content values and obesity. Individuals with metabolic syndrome had the highest water content values in the hypothalamus and the fornix. There is accumulating evidence that inflammation of the hypothalamus contributed to obesity-associated insulin resistance in that area. Whether brain inflammation is a cause or consequence of obesity in humans still needs to be investigated using a longitudinal study design. Using qMRI, we were able to detect marked water content changes in young and older obese adults, which is most likely the result of chronic low-grade inflammation. AU - Kullmann, S. AU - Abbas, Z.* AU - Machann, J. AU - Scheffler, K.* AU - Birkenfeld, A.L. AU - Häring, H.-U. AU - Fritsche, A. AU - Heni, M. C1 - 60277 C2 - 49325 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Investigating obesity-associated brain inflammation using quantitative water content mapping. JO - J. Neuroendocrinol. VL - 32 IS - 12 PB - Wiley PY - 2020 SN - 0953-8194 ER - TY - JOUR AU - Preissl, H. AU - Small, D.* AU - Kullmann, S. C1 - 60882 C2 - 49844 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Neuroendocrinology and brain imaging. JO - J. Neuroendocrinol. VL - 32 IS - 12 PB - Wiley PY - 2020 SN - 0953-8194 ER - TY - JOUR AB - Endothermic mammals and birds require intensive energy turnover to sustain high body temperatures and metabolic rates. To cope with energetic bottlenecks associated with the change of seasons, and to minimise energy expenditure, complex mechanisms and strategies, such as daily torpor and hibernation, are used. During torpor metabolic depression and low body temperatures save energy. However, these bouts of torpor lasting for hours to weeks are interrupted by active 'euthermic' phases with high body temperatures. These dynamic transitions require precise communication between the brain and peripheral tissues to defend rheostasis in energetics, body mass and body temperature. The hypothalamus appears to be the major control centre in the brain, coordinating energy metabolism and body temperature. The sympathetic nervous system controls body temperature by adjustments of shivering and non-shivering thermogenesis, the latter being primarily executed by brown adipose tissue. Over the last decade, comparative physiologists have put forward integrative studies on the ecophysiology, biochemistry and molecular regulation of energy balance in response to seasonal challenges, food availability and ambient temperature. Mammals coping with such environments represent excellent model organisms to study the dynamic regulation of energy metabolism. Beyond the understanding of how animals survive in nature, these studies also uncover general mechanisms of mammalian energy homeostasis. This research will benefit efforts of translational medicine to combat emerging human metabolic disorders. This review focuses on recent advances in the understanding of energy balance and its neuronal and endocrine control during the most extreme metabolic fluctuations in nature: daily torpor and hibernation. AU - Jastroch, M. AU - Giroud, S.* AU - Barrett, P.* AU - Geiser, F.* AU - Heldmaier, G.* AU - Herwig, A.* C1 - 49763 C2 - 40932 CY - Hoboken TI - Seasonal control of mammalian energy balance: Recent advances in the understanding of daily torpor and hibernation. JO - J. Neuroendocrinol. VL - 28 IS - 11 PB - Wiley PY - 2016 SN - 0953-8194 ER - TY - JOUR AB - Thus far, little is known about insulin action in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate brain insulin action in humans providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of brain insulin action was first identified linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. While MEG is a suitable tool to measure brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus insulin action can be detected within all eating behavior relevant regions, which include regions deeply located within the brain as the hypothalamus, midbrain and brainstem as well as regions within the striatum. In this review, we will outline recent advances in the field of neuroimaging to investigate insulin action in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin induced attenuation predominantly in occipital and prefrontal cortical regions and the hypothalamus, successfully localizing insulin sensitive brain regions in healthy mostly normal-weight individuals. However, further studies are needed to localize brain areas affected by insulin resistance in obese individuals, which is an important prerequisite to selectively target brain insulin resistance in obesity. AU - Kullmann, S. AU - Heni, M. AU - Fritsche, A. AU - Preissl, H. C1 - 43102 C2 - 36060 CY - Hoboken SP - 419-423 TI - Insulin action in the human brain: Evidence from neuroimaging studies. JO - J. Neuroendocrinol. VL - 27 IS - 6 PB - Wiley-blackwell PY - 2015 SN - 0953-8194 ER - TY - JOUR AB - Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of the Growth Hormone Secretagogue Receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release, however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad libitum fed male germline goat(-/-) mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat(-/-) mice when compared to age-matched wild-type (WT) mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. While loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of IGF-1 were elevated in goat(-/-) mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat(-/-) mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. While the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF-1 release and growth in goat(-/-) mice. This article is protected by copyright. All rights reserved. AU - Xie, T.Y.* AU - Ngo, S.T.* AU - Veldhuis, J.D.* AU - Jeffery, P.L.* AU - Chopin, L.K.* AU - Tschöp, M.H. AU - Waters, M.J.* AU - Tolle, V.* AU - Epelbaum, J.* AU - Chen, C.C.* AU - Steyn, F.J.* C1 - 47254 C2 - 40618 SP - 872-886 TI - Effect of deletion of ghrelin-o-acyltransferase on the pulsatile release of growth hormone in mice. JO - J. Neuroendocrinol. VL - 27 IS - 12 PY - 2015 SN - 0953-8194 ER -