The mammalian body possesses remarkable adaptability to cold exposure, involving intricate adjustments in cellular metabolism, ultimately leading to thermogenesis. However, cold-induced stress can impact immune response, primarily through noradrenaline-mediated pathways. In our study, we utilized a rat model subjected to short-term or long-term mild cold exposure to investigate systemic immune response during the cold acclimation. To provide human relevance, we included a group of regular cold swimmers in our study. Our research revealed complex relationship between cold exposure, neural signaling, immune response, and thermogenic regulation. One-day cold exposure triggered stress response, including cytokine production in white adipose tissue, subsequently activating brown adipose tissue, and inducing thermogenesis. We further studied systemic immune response, including the proportion of leukocytes and cytokines production. Interestingly, γδ T cells emerged as possible regulators in the broader systemic response, suggesting their possible contribution in the dynamic process of cold adaptation. We employed RNA-seq to gain further insights into the mechanisms by which γδ T cells participate in the response to cold. Additionally, we challenged rats exposed to cold with the Toll-like receptor 2 agonist, showing significant modulation of immune response. These findings significantly contribute to understanding of the physiological acclimation that occur in response to cold exposure.
- MeSH
- aklimatizace imunologie MeSH
- cytokiny metabolismus MeSH
- hnědá tuková tkáň imunologie metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- nízká teplota * MeSH
- receptory antigenů T-buněk gama-delta imunologie metabolismus MeSH
- T-lymfocyty imunologie MeSH
- termogeneze imunologie MeSH
- toll-like receptor 2 * metabolismus genetika imunologie MeSH
- zánět * imunologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Warm-blooded animals such as birds and mammals are able to protect stable body temperature due to various thermogenic mechanisms. These processes can be facultative (occurring only under specific conditions, such as acute cold) and adaptive (adjusting their capacity according to long-term needs). They can represent a substantial part of overall energy expenditure and, therefore, affect energy balance. Classical mechanisms of facultative thermogenesis include shivering of skeletal muscles and (in mammals) non-shivering thermogenesis (NST) in brown adipose tissue (BAT), which depends on uncoupling protein 1 (UCP1). Existence of several alternative thermogenic mechanisms has been suggested. However, their relative contribution to overall heat production and the extent to which they are adaptive and facultative still needs to be better defined. Here we focus on comparison of NST in BAT with thermogenesis in skeletal muscles, including shivering and NST. We present indications that muscle NST may be adaptive but not facultative, unlike UCP1-dependent NST. Due to its slow regulation and low energy efficiency, reflecting in part the anatomical location, induction of muscle NST may counteract development of obesity more effectively than UCP1-dependent thermogenesis in BAT.
- MeSH
- chvění * fyziologie MeSH
- energetický metabolismus fyziologie MeSH
- fyziologická adaptace * fyziologie MeSH
- hnědá tuková tkáň * metabolismus MeSH
- kosterní svaly * metabolismus MeSH
- lidé MeSH
- obezita * metabolismus patofyziologie MeSH
- termogeneze * fyziologie MeSH
- uncoupling protein 1 metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Our circadian world shapes much of metabolic physiology. In mice ∼40% of the light and ∼80% of the dark phase time is characterized by bouts of increased energy expenditure (EE). These ultradian bouts have a higher body temperature (Tb) and thermal conductance and contain virtually all of the physical activity and awake time. Bout status is a better classifier of mouse physiology than photoperiod, with ultradian bouts superimposed on top of the circadian light/dark cycle. We suggest that the primary driver of ultradian bouts is a brain-initiated transition to a higher defended Tb of the active/awake state. Increased energy expenditure from brown adipose tissue, physical activity, and cardiac work combine to raise Tb from the lower defended Tb of the resting/sleeping state. Thus, unlike humans, much of mouse metabolic physiology is episodic with large ultradian increases in EE and Tb that correlate with the active/awake state and are poorly aligned with circadian cycling.
- MeSH
- bdění fyziologie MeSH
- cirkadiánní rytmus * fyziologie MeSH
- energetický metabolismus * fyziologie MeSH
- fotoperioda * MeSH
- hnědá tuková tkáň metabolismus fyziologie MeSH
- myši MeSH
- spánek fyziologie MeSH
- tělesná teplota * fyziologie MeSH
- ultradiánní rytmus * fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl. STUDY DESIGN: Prospective, randomized, blind clinical study. ANIMALS: A total of 120 healthy dogs, aged 2-10 years and weighing 5-20 kg. METHODS: Dogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg-1), MF group with medetomidine (0.005 mg kg-1) and fentanyl (0.01 mg kg-1) and AF group with acepromazine (0.01 mg kg-1) and fentanyl (0.01 mg kg-1). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen-air mixture. Fentanyl was administered continuously (0.01 mg kg-1 hour-1). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10-T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05). RESULTS: Median T-Oeso was significantly higher in MF group between T0-T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60). CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine-fentanyl. However, this difference was not clinically significant.
- MeSH
- acepromazin * farmakologie aplikace a dávkování MeSH
- anestetika intravenózní farmakologie aplikace a dávkování MeSH
- celková anestezie veterinární MeSH
- ezofágus účinky léků MeSH
- fentanyl * farmakologie aplikace a dávkování MeSH
- kombinace anestetik aplikace a dávkování farmakologie MeSH
- medetomidin * farmakologie aplikace a dávkování MeSH
- premedikace anestezie veterinární MeSH
- prospektivní studie MeSH
- psi MeSH
- rektum MeSH
- tělesná teplota * účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- psi MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie veterinární MeSH
Introduction: Thermoregulation is a complex process in the human body with the ability to maintain a constant optimal body temperature. Biochemical processes of the organism, as well as metabolic processes, are closely correlated with body temperature. Human temperature is determined by several laws, in particular metabolic production and heat flow between the organism and the environment. For the proper functioning of the organs in the human body, it is essential to maintain a constant optimum body temperature. This can be disturbed by inadequate internal and external factors and thermal discomfort can affect the patient's overall outcome. Aim: The aim of this study is to evaluate the development of body temperature in critically ill patients in the emergency department and its effect on overall patient outcome. Design: Quasi-experiment. Methods: Direct observation was performed, including measurement and analysis of body temperature in patients with serious condition in emergency admission. Data were collected in the emergency department of a teaching hospital with a trauma center status between March and December 2021. Statistical tests were evaluated at the level of statistical significance α=0.05. Results: The study population consisted of 274 (100%) patients. Most negative readings were recorded at the time of patient admission. During the course of treatment, there was a gradual adjustment of body temperature to the physiological limit. The resulting body temperature values were within the desired or expected parameters. In terms of a more detailed description, the most significant values were identified in patients with cardiac problems. Conclusions: Knowing the direction of body temperature skew can be considered beneficial. Early correction of pathological values can have a major effect on the overall outcome of the patient.
The cardiovascular system is primarily controlled by the autonomic nervous system, and any changes in sympathetic or parasympathetic activity also have an impact on myocardial activity. Heart rate variability (HRV) is a readily available metric used to assess heart rate control by the autonomic nervous system. HRV can provide information about neural (parasympathetic, sympathetic, reflex) and humoral (hormones, thermoregulation) control of myocardial activity. Because there are no relevant reference values for HRV parameters in rats in the scientific literature, all experimental results are only interpreted on the basis of changes from currently measured control or baseline HRV values, which are, however, significantly different in individual studies. Considering the significant variability of published HRV data, the present study focused primarily on comparing control or baseline HRV values under different conditions in in vivo experiments involving rats. The aim of the study was therefore to assess whether there are differences in the starting values before the experiment itself.
OBJECTIVES: Nuclear receptor interacting protein 1 (NRIP1) suppresses energy expenditure via repression of nuclear receptors, and its depletion markedly elevates uncoupled respiration in mouse and human adipocytes. We tested whether NRIP1 deficient adipocytes implanted into obese mice would enhance whole body metabolism. Since β-adrenergic signaling through cAMP strongly promotes adipocyte thermogenesis, we tested whether the effects of NRIP1 knock-out (NRIP1KO) require the cAMP pathway. METHODS: NRIP1KO adipocytes were implanted in recipient high-fat diet (HFD) fed mice and metabolic cage studies conducted. The Nrip1 gene was disrupted by CRISPR in primary preadipocytes isolated from control vs adipose selective GsαKO (cAdGsαKO) mice prior to differentiation to adipocytes. Protein kinase A inhibitor was also used. RESULTS: Implanting NRIP1KO adipocytes into HFD fed mice enhanced whole-body glucose tolerance by increasing insulin sensitivity, reducing adiposity, and enhancing energy expenditure in the recipients. NRIP1 depletion in both control and GsαKO adipocytes was equally effective in upregulating uncoupling protein 1 (UCP1) and adipocyte beiging, while β-adrenergic signaling by CL 316,243 was abolished in GsαKO adipocytes. Combining NRIP1KO with CL 316,243 treatment synergistically increased Ucp1 gene expression and increased the adipocyte subpopulation responsive to beiging. Estrogen-related receptor α (ERRα) was dispensable for UCP1 upregulation by NRIPKO. CONCLUSIONS: The thermogenic effect of NRIP1 depletion in adipocytes causes systemic enhancement of energy expenditure when such adipocytes are implanted into obese mice. Furthermore, NRIP1KO acts independently but cooperatively with the cAMP pathway in mediating its effect on adipocyte beiging.
- MeSH
- lidé MeSH
- myši obézní MeSH
- myši MeSH
- nuclear receptor interacting protein 1 metabolismus MeSH
- obezita metabolismus MeSH
- signální transdukce * MeSH
- termogeneze genetika MeSH
- tukové buňky * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Horúčka je častým javom na neurologických jednotkách intenzívnej starostlivosti. Etiologicky najčastejšie ide o infekčnú príčinu, v menšej miere prichádzajú následne do úvahy neinfekčné príčiny, ako trombembolizmus, medikamentózne navodený stav, postoperačné príčiny a v neposlednom rade centrálna neurogénna hypertermia. Ide o diagnózu per exclusionem, ktorá doteraz nemá štandardizované diagnostické kritériá ani liečbu. Rovnako tak nie je úplne objasnený ani patomechanizmus jej vzniku. Článok sa zaoberá prehľadom dostupných údajov o fyziológii termoregulácie, predostiera predpokladaný patofyziologický pôvod danej entity (s dôrazom na problematiku z pohľadu neurológa), zmieňuje sa o prejavoch a dôsledkoch ochorenia, napokon uvádza stručný prehľad možností liečby vrátane off‐label preparátov.
Fever is a common phenomenon within neurological intensive care units. Etiologically, it is most often an infectious cause, to a lesser extent, non-infectious causes come into consideration such as thromboembolism, medically induced condition, postoperative causes and, last but not least, central neurogenic hyperthermia. This is a diagnosis per exclusionem, which does not yet have standardized diagnostic criteria or treatment. Likewise, the pathomechanism of its formation is not fully clarified. The article deals with an overview of available data from the physiology of thermoregulation, lays out the presumed pathophysiological background of the given entity (with an emphasis on the issue from the neurologist's point of view), mentions the symptoms and consequences of the disease, and finally gives a brief overview of treatment options, including off-label preparations.
- MeSH
- hypertermie * diagnóza etiologie farmakoterapie patofyziologie terapie MeSH
- hypothalamus fyziologie MeSH
- lidé MeSH
- mozek patofyziologie MeSH
- nemoci nervového systému klasifikace patofyziologie MeSH
- neurony fyziologie klasifikace MeSH
- rizikové faktory MeSH
- tělesná teplota fyziologie MeSH
- termoregulace fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
Disruption of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) in mice induces browning in inguinal white adipose tissue (iWAT). However, adipocyte FASN knockout (KO) increases acetyl-coenzyme A (CoA) and malonyl-CoA in addition to depletion of palmitate. We explore which of these metabolite changes triggers adipose browning by generating eight adipose-selective KO mouse models with loss of ATP-citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), ACC2, malonyl-CoA decarboxylase (MCD) or FASN, or dual KOs ACLY/FASN, ACC1/FASN, and ACC2/FASN. Preventing elevation of acetyl-CoA and malonyl-CoA by depletion of adipocyte ACLY or ACC1 in combination with FASN KO does not block the browning of iWAT. Conversely, elevating malonyl-CoA levels in MCD KO mice does not induce browning. Strikingly, adipose ACC1 KO induces a strong iWAT thermogenic response similar to FASN KO while also blocking malonyl-CoA and palmitate synthesis. Thus, ACC1 and FASN are strong suppressors of adipocyte thermogenesis through promoting lipid synthesis rather than modulating the DNL intermediates acetyl-CoA or malonyl-CoA.
- MeSH
- acetyl-CoA-karboxylasa * metabolismus MeSH
- acetylkoenzym A metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- palmitany metabolismus MeSH
- syntázy mastných kyselin metabolismus MeSH
- termogeneze MeSH
- tukové buňky * metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
OBJECTIVE: The metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis. METHODS: We used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology. RESULTS: ADAM17adipoq-creΔ/Δ mice exhibited a hypermetabolic phenotype characterized by elevated energy consumption and increased levels of adipocyte thermogenic gene expression. On a high fat diet, these mice were more thermogenic, while exhibiting elevated expression levels of genes associated with lipid oxidation and lipolysis. This hypermetabolic phenotype protected mutant mice from obesogenic challenge, limiting weight gain, hepatosteatosis and insulin resistance. Activation of beta-adrenoceptors by the neurotransmitter norepinephrine, a key regulator of adipocyte physiology, triggered the shedding of ADAM17 substrates, and regulated ADAM17 expression at the mRNA and protein levels, hence identifying a functional connection between thermogenic licensing and the regulation of ADAM17. Proteomic studies identified Semaphorin 4B (SEMA4B), as a novel ADAM17-shed adipokine, whose expression is regulated by physiological thermogenic cues, that acts to inhibit adipocyte differentiation and dampen thermogenic responses in adipocytes. Transcriptomic data showed that cleaved SEMA4B acts in an autocrine manner in brown adipocytes to repress the expression of genes involved in adipogenesis, thermogenesis, and lipid uptake, storage and catabolism. CONCLUSIONS: Our findings identify a novel ADAM17-dependent axis, regulated by beta-adrenoceptors and mediated by the ADAM17-cleaved form of SEMA4B, that modulates energy balance in adipocytes by inhibiting adipocyte differentiation, thermogenesis and lipid catabolism.
- MeSH
- adipokiny * metabolismus MeSH
- beta-adrenergní receptory metabolismus MeSH
- buněčná diferenciace MeSH
- hnědé tukové buňky metabolismus MeSH
- lipidy MeSH
- myši MeSH
- proteomika MeSH
- semaforiny * genetika metabolismus MeSH
- termogeneze fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
