Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

OBJECTIVE: To observe the effect of electroacupuncture (EA) on laparoscope postoperative shivering in patients undergoing general anesthesia and explore its effect mechanism. METHODS: A total of 80 patients with elective laparoscopic resection of intestinal tumor under general anesthesia were randomly divided into an EA group and a tramadol group, 40 cases in each group. Thirty min prior to the end of the operation, in the EA group, EA was exerted at Neimadian and Zusanli (ST 36), with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in intensity, and lasting 30 min. In the tramadol group, tramadol hydrochloride injection was dropped intravenously, 1 mg/kg. The conditions of shivering, dizziness, nausea, vomiting and agitation were observed in the post-anesthesia care unit (PACU). Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were observed before treatment (T₀), at the moment of extubation (T₁), in 3 min of extubation (T₂) and 1 h after operation (T₃). Using ELISA, at T₀ and T₃, the expression levels of interleukin 6 (IL-6) and 5-hydroxytryptamine (5-HT) in plasma were detected separately. Choking and agitation were recorded during extubation. RESULTS: ① In the EA group, the incidence of shivering, dizziness, nausea, vomiting and agitation in the PACU was lower than that in the tramadol group (P<0.05). ②Compared with T₀, HR, SBP and DBP were increased at T₁ and T₂ in the tramadol group (P<0.05). HR, SBP and DBP in the EA group were lower than the tramadol group at T₁ and T₂ (P<0.05). ③Compared with T₀, the expression levels of IL-6 and 5-HT in plasma were increased at T₃ in the tramadol group (P<0.05). The expression levels of IL-6 and 5-HT in the EA group were lower than the tramadol group at T₃ (P<0.05). ④The incidence of choking and agitation during exudation in the EA group was lower than that in the tramadol group (P<0.05). CONCLUSION Electroacupuncture can reduce the incidence of laparoscopic postoperative shivering under general anesthesia. The potential mechanism mays related to the modulation of the expression levels of IL-6 and 5-HT caused by surgical trauma.
Anesthesia, General/adverse effects* ; Electroacupuncture ; Humans ; Laparoscopes ; Postoperative Period ; Shivering

β3-adrenergic agonists induce adaptive thermogenesis and promote beiging of white fat. However, it remains unclear which metabolites mediate the stimulatory effects of β3-adrenergic agonists on thermogenesis of brown and beige fat. In this study, adipose tissue was isolated from 8-week-old C57/BL6J male mice by intraperitoneal administration of β3-adrenergic agonist CL316,243 for RNA-Seq, which revealed that histidine decarboxylase, a key enzyme in histamine synthesis, was strongly induced in adipose by CL316,243. Therefore, we speculated that histamine might be involved in the process of thermogenesis in adipose tissue. We determined the physiological role and mechanism by which histamine promotes fat thermogenesis by intravenous administering histamine to C57BL/6J mice fed a normal or a high-fat diet. The results showed that intravenous injection of histamine into C57BL/6J mice fed a normal diet stimulated the expression of thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1), in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). H&E staining also suggested that histamine treatment decreased the size of lipid droplets in adipocytes. Moreover, histamine treatment also enhanced thermogenesis of fat in high-fat diet induced obese mice, and improved glucose intolerance and fatty liver phenotype. Finally, we demonstrated that the effects of histamine on the thermogenic program were cell autonomous. Our data suggest that histamine may mediate the effects of β3-adrenergic agonists on thermogenesis of fat.
Adipose Tissue, Beige ; Adipose Tissue, Brown ; Animals ; Histamine ; Male ; Mice ; Mice, Inbred C57BL ; Thermogenesis ; Uncoupling Protein 1/genetics*

BACKGROUND: Hypothermia below 36℃ is a common problem during arthroscopic shoulder surgery. Geriatric patients are more vulnerable to perioperative hypothermia. The present study compared postoperative hypothermia between geriatric and young adult patients receiving arthroscopic shoulder surgery. METHODS: Data were collected retrospectively from a geriatric group (aged 65 or more, n = 29), and a control group (aged 19–64, n = 33) using the anesthesia records of patients who had undergone arthroscopic shoulder surgery. The primary outcome measure was the incidence of hypothermia upon arrival in the postanesthesia care unit (PACU). The secondary outcome measure was the decrease in body temperature from admission into the operating room to admission into the PACU. RESULTS: The incidence of hypothermia was 93.1% and 54.5% in the geriatric and control groups, respectively, demonstrating a significant difference between the groups (P < 0.001). Comparison between body temperature revealed a decrease of 1.5 ± 0.6℃ and 1.0 ± 0.4℃ in the geriatric and control groups, respectively, showing a significant difference between the groups (P < 0.001). The degree of hypothermia was significantly different between the groups (P = 0.027). No shivering was observed in either of the two groups, but the incidence of thermal discomfort was higher in the geriatric group than in the control group (P = 0.021). CONCLUSIONS: In geriatric patients undergoing arthroscopic shoulder surgery, both the incidence of postoperative hypothermia and the associated temperature drop are more prominent than those in young adult patients. Additional warming methods will be needed to prevent postoperative hypothermia in geriatric patients.
Anesthesia ; Arthroscopy ; Body Temperature ; Humans ; Hypothermia* ; Incidence ; Operating Rooms ; Outcome Assessment (Health Care) ; Retrospective Studies ; Shivering ; Shoulder* ; Young Adult

BACKGROUND: At least 30 minutes of pre-warming has been recommended for the prevention of redistribution hypothermia. However, it has been reported that less than 30 minutes of pre-warming is also effective. The aim of this study was to evaluate the ability of 10 minutes of pre-warming to prevent inadvertent perioperative hypothermia. Results were compared with 30 minutes of pre-warming. METHODS: In this prospective randomized study, 59 patients scheduled for elective surgery less than 120 minutes under general anesthesia were divided into 2 groups: the first group was pre-warmed for 10 minutes (n = 30), the second group for 30 minutes (n = 29). The patients were pre-warmed for 10 or 30 minutes in the pre-anesthetic area using a forced-air warmer. When the patients' body temperatures decreased below 36℃, we warmed them with a forced-air warmer intraoperatively and postoperatively. Body temperatures were recorded during perioperative periods. Shivering and thermal comfort were evaluated in the pre-anesthetic area and post-anesthesia care unit. RESULTS: The incidence of intraoperative and postoperative hypothermia were not significantly different (P > 0.05). However, the temperatures were higher in the 30 minute group from the post-warming time to 90 minutes after anesthetic induction (P < 0.05). CONCLUSIONS: Ten minutes of pre-warming has the same effectiveness as 30 minutes of pre-warming for preventing inadvertent perioperative hypothermia. It is a preferable choice for the patients scheduled for surgery less than 120 minutes under general anesthesia.
Anesthesia, General ; Body Temperature ; Humans ; Hypothermia* ; Incidence ; Perioperative Period ; Prospective Studies ; Shivering

Brown adipose tissue (BAT) plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue (WAT), have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BATactivation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.
Adipose Tissue, Brown ; metabolism ; Aging ; metabolism ; Animals ; Cachexia ; metabolism ; pathology ; Disease Models, Animal ; Energy Metabolism ; Humans ; Metabolic Syndrome ; metabolism ; Neoplasms ; metabolism ; pathology ; Obesity ; metabolism ; Thermogenesis

Given that increased thermogenesis in white adipose tissue, also known as browning, promotes energy expenditure, significant efforts have been invested to determine the molecular factors involved in this process. Here we show that HOXC10, a homeobox domain-containing transcription factor expressed in subcutaneous white adipose tissue, is a suppressor of genes involved in browning white adipose tissue. Ectopic expression of HOXC10 in adipocytes suppresses brown fat genes, whereas the depletion of HOXC10 in adipocytes and myoblasts increases the expression of brown fat genes. The protein level of HOXC10 inversely correlates with brown fat genes in subcutaneous white adipose tissue of cold-exposed mice. Expression of HOXC10 in mice suppresses cold-induced browning in subcutaneous white adipose tissue and abolishes the beneficial effect of cold exposure on glucose clearance. HOXC10 exerts its effect, at least in part, by suppressing PRDM16 expression. The results support that HOXC10 is a key negative regulator of the process of browning in white adipose tissue.
Adipocytes ; Adipose Tissue, Brown ; Adipose Tissue, White ; Animals ; Ectopic Gene Expression ; Energy Metabolism ; Genes, Homeobox ; Glucose ; Mice ; Myoblasts ; Thermogenesis ; Transcription Factors

We presented a patient with cerebral decompression sickness, who showed predominant vasogenic edema on a 3.0 Tesla (3T) magnetic resonance imaging (MRI) findings, including diffusion-weighted image (DWI) and apparent diffusion coefficient (ADC) mapping. Within minutes of surfacing, he developed paresis of the right lower limb. During transport, he began shivering, followed by severe spasm that eventually progressed to a tonic-clonic seizure. Emergent hyperbaric oxygen therapy (HBOT) was performed with U.S. Navy treatment table 6A after a treatment of seizure activity. Brain MRI was performed after hyperbaric oxygen therapy to detect any cerebral lesions, which showed subcortical hyperintensity signal changes in the left fronto-parietal region on the ADC map. Overlying cortical hyperintensity on DWI sequences and cortical hypointensity on the ADC map were simultaneously observed. Moreover, these findings disappeared in a followup MRI with complete resolution of symptoms. These findings indicate that vasogenic edema can cause cerebral decompression sickness (DCS) and that 3T MRI with DWI and ADC mapping may be useful for diagnosing cerebral DCS. In addition, these findings suggest that DW-MRI may also be useful in predicting the prognosis of cerebral DCS.
Brain ; Brain Edema ; Decompression Sickness* ; Decompression* ; Diffusion ; Diffusion Magnetic Resonance Imaging ; Edema ; Follow-Up Studies ; Humans ; Hyperbaric Oxygenation ; Lower Extremity ; Magnetic Resonance Imaging* ; Paresis ; Prognosis ; Seizures ; Shivering ; Spasm

PURPOSE: Oral naloxone is combined with oxycodone to alleviate or prevent opioid-induced constipation in cancer pain patients. However, there is still concern that oral naloxone may precipitate opioid withdrawal symptoms in patients on opioids. We retrospectively investigated clinical characteristics of cancer patients who experienced opioid withdrawal symptoms. METHODS: We reviewed medical records of all patients who were prescribed with oral oxycodone/naloxone at a tertiary cancer center from January 1, 2012 through December 31, 2016. Eligible patients were screened based on demographics, opioid and naloxone dosages, clinical manifestation and pain intensity. RESULTS: Among a total of 1,641 patients, 10 patients were selected. Seven patients were male, and the average age was 68.1 years. The median dose of naloxone that induced withdrawal symptoms was 20 mg. Most common withdrawal symptom was shivering (seven patients) followed by cold sweating (five), and muscle twitching (five). Other symptoms included restlessness, fever, dizziness, and yawning. Pain was exacerbated from the median intensity of numeric rating scale (NRS) 3 to NRS 6. CONCLUSION: Opioid withdrawal symptoms may occur when switching to oral oxycodone/naloxone for cancer patients who have been treated with other strong opioids. A prospective, multicenter study on this issue should be conducted in future.
Analgesics, Opioid* ; Constipation ; Demography ; Dizziness ; Fever ; Humans ; Male ; Medical Records ; Naloxone ; Oxycodone ; Prospective Studies ; Psychomotor Agitation ; Retrospective Studies ; Shivering ; Substance Withdrawal Syndrome* ; Sweat ; Sweating ; Yawning

Obesity and diabetes has become a major epidemic across the globe. Controlling obesity has been a challenge since this would require either increased physical activity or reduced caloric intake; both are difficult to enforce. There has been renewed interest in exploiting pathways such as uncoupling protein 1 (UCP1)-mediated uncoupling in brown adipose tissue (BAT) and white adipose tissue to increase energy expenditure to control weight gain. However, relying on UCP1-based thermogenesis alone may not be sufficient to control obesity in humans. On the other hand, skeletal muscle is the largest organ and a major contributor to basal metabolic rate and increasing energy expenditure in muscle through nonshivering thermogenic mechanisms, which can substantially affect whole body metabolism and weight gain. In this review we will describe the role of Sarcolipin-mediated uncoupling of Sarcoplasmic Reticulum Calcium ATPase (SERCA) as a potential mechanism for increased energy expenditure both during cold and diet-induced thermogenesis.
Adipose Tissue, Brown ; Adipose Tissue, White ; Basal Metabolism ; Diabetes Mellitus ; Energy Intake ; Energy Metabolism* ; Hand ; Humans ; Metabolism ; Motor Activity ; Muscle, Skeletal* ; Obesity ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; Thermogenesis* ; Weight Gain