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Hypothalamus-skeletal muscle crosstalk during exercise and its role in metabolism modulation.
Ibeas, K, Herrero, L, Mera, P, Serra, D
Biochemical pharmacology. 2021;:114640
Abstract
Physical inactivity is a major public health problem that contributes to the development of several pathologies such as obesity, type 2 diabetes and cardiovascular diseases. Regular exercise mitigates the progression of these metabolic problems and contributes positively to memory and behavior. Therefore, public health agencies have incorporated exercise in the treatment of widespread disorders. The hypothalamus, specifically the ventromedial and the arcuate nuclei, responds to exercise activity and modulates energy metabolism through stimulation of the sympathetic nervous system and catecholamine secretion into the circulation. In addition, physical performance enhances cognitive functions and memory, mediated mostly by an increase in brain-derived neurotrophic factor levels in brain. During exercise training, skeletal muscle myofibers remodel their biochemical, morphological and physiological state. Moreover, skeletal muscle interacts with other organs by the release into the circulation of myokines, molecules that exhibit autocrine, paracrine and endocrine functions. Several studies have focused on the role of skeletal muscle and tissues in response to physical activity. However, how the hypothalamus could influence the skeletal muscle task in the context of exercise is less studied. Here, we review recent data about hypothalamus-skeletal muscle crosstalk in response to physical activity and focus on specific aspects such as the neuroendocrinological effects of exercise and the endocrine functions of skeletal muscle, to provide a perspective for future study directions.
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Mechanism of Action of Acupuncture in Obesity: A Perspective From the Hypothalamus.
Wang, L, Yu, CC, Li, J, Tian, Q, Du, YJ
Frontiers in endocrinology. 2021;:632324
Abstract
Obesity is a prevalent metabolic disease caused by an imbalance in food intake and energy expenditure. Although acupuncture is widely used in the treatment of obesity in a clinical setting, its mechanism has not been adequately elucidated. As the key pivot of appetite signals, the hypothalamus receives afferent and efferent signals from the brainstem and peripheral tissue, leading to the formation of a complex appetite regulation circuit, thereby effectively regulating food intake and energy homeostasis. This review mainly discusses the relationship between the hypothalamic nuclei, related neuropeptides, brainstem, peripheral signals, and obesity, as well as mechanisms of acupuncture on obesity from the perspective of the hypothalamus, exploring the current evidence and therapeutic targets for mechanism of action of acupuncture in obesity.
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A multi-parameter study of the etiological diagnosis of hyponatremia after hypothalamic tumor surgery.
Yang, F, Cao, Z, Wang, X, Cui, Z, Cheng, D, Li, Z, Lv, B, Zhang, H, Guo, P, Feng, Y, et al
Clinical neurology and neurosurgery. 2021;:106963
Abstract
OBJECTIVES This study aimed to analyze the difference between cerebral salt-wasting syndrome (CSWS) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients with hyponatremia after hypothalamic tumor surgery, and to explore a convenient and effective way to identify CSWS and SIADH. METHODS Patients undergoing craniotomy of hypothalamic tumor admitted to the Department of The Affiliated Hospital of Qingdao University from December 2018 to May 2020 were enrolled in this study. Plasma brain natriuretic peptide (BNP), 24-h urine sodium, 24-h urine volume, and the diameter of the inferior vena cava (IVCD) were measured daily before operation and 1-7 days after operation, to analyze differences in plasma BNP, 24-h urinary sodium excretion, 24-h urine volume, and IVCD between the CSWS and SIADH. RESULTS The medical data of 31 patients with hypothalamic tumors were collected. Fifteen of these patients (48%) had postoperative hyponatremia, nine patients (29%) had CSWS, and six patients (19%) had SIADH. Plasma BNP, 24-h urinary sodium excretion, and 24-h urine volume in the CSWS group were significantly higher than those in the SIADH group. IVCD decreased in the CSWS group and increased in the SIADH group. CONCLUSIONS When hyponatremia occurs after hypothalamic tumor surgery, plasma BNP, 24-h urinary sodium excretion, 24-h urine volume, and IVCD are of great help in identifying CSWS and SIADH.
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Hypothalamic NAD+-Sirtuin Axis: Function and Regulation.
Roh, E, Kim, MS
Biomolecules. 2020;(3)
Abstract
The rapidly expanding elderly population and obesity endemic have become part of continuing global health care problems. The hypothalamus is a critical center for the homeostatic regulation of energy and glucose metabolism, circadian rhythm, and aging-related physiology. Nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase sirtuins are referred to as master metabolic regulators that link the cellular energy status to adaptive transcriptional responses. Mounting evidence now indicates that hypothalamic sirtuins are essential for adequate hypothalamic neuronal functions. Owing to the NAD+-dependence of sirtuin activity, adequate hypothalamic NAD+ contents are pivotal for maintaining energy homeostasis and circadian physiology. Here, we comprehensively review the regulatory roles of the hypothalamic neuronal NAD+-sirtuin axis in a normal physiological context and their changes in obesity and the aging process. We also discuss the therapeutic potential of NAD+ biology-targeting drugs in aging/obesity-related metabolic and circadian disorders.
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Microbiota in obesity: interactions with enteroendocrine, immune and central nervous systems.
Mulders, RJ, de Git, KCG, Schéle, E, Dickson, SL, Sanz, Y, Adan, RAH
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2018;(4):435-451
Abstract
Western diets, with high consumption of simple sugars and saturated fats, contribute to the rise in the prevalence of obesity. It now seems clear that high-fat diets cause obesity, at least in part, by modifying the composition and function of the microorganisms that colonize in the gastrointestinal tract, the microbiota. The exact pathways by which intestinal microbiota contribute to obesity remain largely unknown. High-fat diet-induced alterations in intestinal microbiota have been suggested to increase energy extraction, intestinal permeability and systemic inflammation while decreasing the capability to generate obesity-suppressing short-chain fatty acids. Moreover, by increasing systemic inflammation, microglial activation and affecting vagal nerve activity, 'obese microbiota' indirectly influence hypothalamic gene expression and promote overeating. Because the potential of intestinal microbiota to induce obesity has been recognized, multiple ways to modify its composition and function are being investigated to provide novel preventive and therapeutic strategies against diet-induced obesity.
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The effect of consumption temperature on the homeostatic and hedonic responses to glucose ingestion in the hypothalamus and the reward system.
van Opstal, AM, van den Berg-Huysmans, AA, Hoeksma, M, Blonk, C, Pijl, H, Rombouts, SARB, van der Grond, J
The American journal of clinical nutrition. 2018;(1):20-25
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Abstract
BACKGROUND Excessive consumption of sugar-sweetened beverages (SSBs) has been associated with obesity and related diseases. SSBs are often consumed cold, and both the energy content and temperature might influence the consumption behavior for SSBs. OBJECTIVE The main aim of this study was to elucidate whether consumption temperature and energy (i.e., glucose) content modulate homeostatic (hypothalamus) and reward [ventral tegmental area (VTA)] responses. DESIGN Sixteen healthy men participated in our study [aged 18-25 y; body mass index (kg/m2): 20-23]. High-resolution functional magnetic resonance imaging data were collected after ingestion of 4 different study stimuli: plain tap water at room temperature (22°C), plain tap water at 0°C, a glucose-containing beverage (75 g glucose dissolved in 300 mL water) at 22°C, and a similar glucose drink at 0°C. Blood oxygen level-dependent (BOLD) changes from baseline (7 min preingestion) were analyzed over time in the hypothalamus and VTA for individual stimulus effects and for effects between stimuli. RESULTS In the hypothalamus, water at 22°C led to a significantly increased BOLD response; all other stimuli resulted in a direct, significant decrease in BOLD response compared with baseline. In the VTA, a significantly decreased BOLD response compared with baseline was found after the ingestion of stimuli containing glucose at 0°C and 22°C. These responses were not significantly modulated by consumption temperature. The consumption of plain water did not have a significant VTA BOLD effect. CONCLUSIONS Our data show that glucose at 22°C, glucose at 0°C, and water at 0°C lowered hypothalamic activity, which is associated with increased satiation. On the contrary, the consumption of water at room temperature increased activity. All stimuli led to a similar VTA response, which suggests that all drinks elicited a similar hedonic response. Our results indicate that, in addition to glucose, the low temperature at which SSBs are often consumed also leads to a response from the hypothalamus and might strengthen the response of the VTA. This trial was registered at www.clinicaltrials.gov as NCT03181217.
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Post mortem single-cell labeling with DiI and immunoelectron microscopy unveil the fine structure of kisspeptin neurons in humans.
Takács, S, Bardóczi, Z, Skrapits, K, Göcz, B, Váczi, V, Maglóczky, Z, Szűcs, I, Rácz, G, Matolcsy, A, Dhillo, WS, et al
Brain structure & function. 2018;(5):2143-2156
Abstract
Kisspeptin (KP) synthesizing neurons of the hypothalamic infundibular region are critically involved in the central regulation of fertility; these cells regulate pulsatile gonadotropin-releasing hormone (GnRH) secretion and mediate sex steroid feedback signals to GnRH neurons. Fine structural analysis of the human KP system is complicated by the use of post mortem tissues. To gain better insight into the neuroanatomy of the somato-dendritic cellular compartment, we introduced the diolistic labeling of immunohistochemically identified KP neurons using a gene gun loaded with the lipophilic dye, DiI. Confocal microscopic studies of primary dendrites in 100-µm-thick tissue sections established that 79.3% of KP cells were bipolar, 14.1% were tripolar, and 6.6% were unipolar. Primary dendrites branched sparsely, contained numerous appendages (9.1 ± 1.1 spines/100 µm dendrite), and received rich innervation from GABAergic, glutamatergic, and KP-containing terminals. KP neuron synaptology was analyzed with immunoelectron microscopy on perfusion-fixed specimens. KP axons established frequent contacts and classical synapses on unlabeled, and on KP-immunoreactive somata, dendrites, and spines. Synapses were asymmetric and the presynaptic structures contained round and regular synaptic vesicles, in addition to dense-core granules. Although immunofluorescent studies failed to detect vesicular glutamate transporter isoforms in KP axons, ultrastructural characteristics of synaptic terminals suggested use of glutamatergic, in addition to peptidergic, neurotransmission. In summary, immunofluorescent and DiI labeling of KP neurons in thick hypothalamic sections and immunoelectron microscopic studies of KP-immunoreactive neurons in brains perfusion-fixed shortly post mortem allowed us to identify previously unexplored fine structural features of KP neurons in the mediobasal hypothalamus of humans.
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A randomized, placebo-controlled trial of beloranib for the treatment of hypothalamic injury-associated obesity.
Shoemaker, A, Proietto, J, Abuzzahab, MJ, Markovic, T, Malloy, J, Kim, DD
Diabetes, obesity & metabolism. 2017;(8):1165-1170
Abstract
AIMS: Hypothalamic injury-associated obesity (HIAO) results from damage to the hypothalamus that often occurs with surgical removal/radiation therapy of tumours in the hypothalamic region, such as craniopharyngioma. There is currently no rigorously studied pharmaceutical treatment for the intractable weight gain and cardiometabolic consequences that occur in patients with HIAO. We aimed to assess efficacy, safety and tolerability of beloranib treatment for 4 to 8 weeks in patients with HIAO. MATERIALS AND METHODS This Phase 2a, double-blind, placebo-controlled study included 14 patients with HIAO, randomized to receive beloranib 1.8 mg or placebo subcutaneously twice weekly for 4 weeks with an optional 4-week open-label extension in which all patients received beloranib. The primary endpoint was change in weight from baseline to Week 4. RESULTS Participants were 64% female, with a mean (SD) age of 32 (9) years, BMI of 43 (7) kg/m2 and weight of 126 (22) kg. Compared with placebo (N = 4), beloranib 1.8 mg (N = 8) resulted in a mean (95% CI) difference in weight of -3.2 (-5.4, -0.9) kg after 4 weeks. Weight loss continued through the 8 weeks in patients randomized to beloranib (mean -6.2 [-8.2, -4.1] kg). Beloranib treatment was associated with improvements in high-sensitivity CRP. Adverse events were mild to moderate. No patients who received beloranib discontinued treatment. CONCLUSION Beloranib treatment resulted in progressive weight loss in patients with HIAO that was comparable to that observed with beloranib in patients with exogenous obesity. These findings indicate a novel mechanism for treating obesity in patients with HIAO.
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Macronutrients and the FTO gene expression in hypothalamus; a systematic review of experimental studies.
Doaei, S, Kalantari, N, Mohammadi, NK, Tabesh, GA, Gholamalizadeh, M
Indian heart journal. 2017;(2):277-281
Abstract
The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article) found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions.
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Altered cross-talk between the hypothalamus and non-homeostatic regions linked to obesity and difficulty to lose weight.
Contreras-Rodríguez, O, Vilar-López, R, Andrews, ZB, Navas, JF, Soriano-Mas, C, Verdejo-García, A
Scientific reports. 2017;(1):9951
Abstract
Interactions between the hypothalamus and non-homeostatic regions may contribute to explain the difficulty to lose weight in obesity, an assumption never tested in human longitudinal studies. We investigated whether the functional connectivity between the medial and lateral hypothalamus (MH and LH) and corticostriatal regions differs between individuals with excess weight (n = 42) and normal weight (n = 39) using a seed-based resting-state approach. In addition, we examined the longitudinal association between functional connectivity and weight loss in a 3-month follow-up diet. Results showed that participants with excess weight had increased connectivity between the MH and the striatum and subgenual anterior cingulate cortex, and decreased connectivity with the middle frontal gyrus, and the bed nucleus of the stria terminalis (BNST), as well as a decreased connectivity between the LH and the cerebellum. Decreased connectivity between the MH and the posterior part of the BNST, and between the LH and the cerebellar cortex, predicted a greater percentage of weight loss. Functional connectivity measures explained 36% of the 3-month weight change among individuals with excess weight. We conclude that altered functional connectivity between homeostatic-hypothalamic regions and non-homeostatic corticostriatal and cerebellar regions is linked to obesity and difficulty to lose weight.