1.Hypoxia‑inducible factor‑1α‑deficient adipose‑tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein‑1
Gi‑Sue KANG ; Young‑Eun KIM ; Ho Rim OH ; Hye‑Ju JO ; Seoyeon BOK ; Yoon Kyung JEON ; Gi Jeong CHEON ; Tae‑Young ROH ; Young‑Tae CHANG ; Do Joong PARK ; G‑One AHN
Laboratory Animal Research 2024;40(4):408-423
Background:
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes.
Results:
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.
Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
2.Hypoxia‑inducible factor‑1α‑deficient adipose‑tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein‑1
Gi‑Sue KANG ; Young‑Eun KIM ; Ho Rim OH ; Hye‑Ju JO ; Seoyeon BOK ; Yoon Kyung JEON ; Gi Jeong CHEON ; Tae‑Young ROH ; Young‑Tae CHANG ; Do Joong PARK ; G‑One AHN
Laboratory Animal Research 2024;40(4):408-423
Background:
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes.
Results:
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.
Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
3.Hypoxia‑inducible factor‑1α‑deficient adipose‑tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein‑1
Gi‑Sue KANG ; Young‑Eun KIM ; Ho Rim OH ; Hye‑Ju JO ; Seoyeon BOK ; Yoon Kyung JEON ; Gi Jeong CHEON ; Tae‑Young ROH ; Young‑Tae CHANG ; Do Joong PARK ; G‑One AHN
Laboratory Animal Research 2024;40(4):408-423
Background:
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes.
Results:
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.
Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
4.Hypoxia‑inducible factor‑1α‑deficient adipose‑tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein‑1
Gi‑Sue KANG ; Young‑Eun KIM ; Ho Rim OH ; Hye‑Ju JO ; Seoyeon BOK ; Yoon Kyung JEON ; Gi Jeong CHEON ; Tae‑Young ROH ; Young‑Tae CHANG ; Do Joong PARK ; G‑One AHN
Laboratory Animal Research 2024;40(4):408-423
Background:
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes.
Results:
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.
Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
5.Hypoxia‑inducible factor‑1α‑deficient adipose‑tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein‑1
Gi‑Sue KANG ; Young‑Eun KIM ; Ho Rim OH ; Hye‑Ju JO ; Seoyeon BOK ; Yoon Kyung JEON ; Gi Jeong CHEON ; Tae‑Young ROH ; Young‑Tae CHANG ; Do Joong PARK ; G‑One AHN
Laboratory Animal Research 2024;40(4):408-423
Background:
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes.
Results:
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.
Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
6.Quality of Acute Stroke Care within Emergency Medical Service System in Korea: Proposal for Severe Emergency Medical Center
Kyung Bok LEE ; Ji Sung LEE ; Jeong-Yoon LEE ; Jun Yup KIM ; Han-Yeong JEONG ; Seong-Eun KIM ; Jonguk KIM ; Do Yeon KIM ; Keon-Joo LEE ; Jihoon KANG ; Beom Joon KIM ; Tae Jung KIM ; Sang Joon AN ; Jang-Hyun BAEK ; Seongheon KIM ; Hyun-Wook NAH ; Jong Yun LEE, ; Jee-Hyun KWON ; Seong Hwan AHN ; Keun-Hwa JUNG ; Hee-Kwon PARK ; Tai Hwan PARK ; Jong-Moo PARK ; Yong-Jin CHO ; Im Seok KOH ; Soo Joo LEE ; Jae-Kwan CHA ; Joung-Ho RHA ; Juneyoung LEE ; Boung Chul LEE ; In Ok BAE ; Gui Ok KIM ; Hee-Joon BAE
Journal of the Korean Neurological Association 2023;41(1):18-30
Background:
Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas.
Methods:
This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis.
Results:
In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively).
Conclusions
There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.
7.What Is Appropriate Upper Endoscopic Interval Among Dyspeptic Patients With Previously Normal Endoscopy? A Multicenter Study With Bayesian Change Point Analysis
Jong Wook KIM ; Kee Wook JUNG ; Joong Goo KWON ; Jung Bok LEE ; Jong Kyu PARK ; Ki Bae BANG ; Chung Hyun TAE ; Jung Hwan OH
Journal of Neurogastroenterology and Motility 2019;25(4):544-550
BACKGROUND/AIMS: Appropriate interval for performing follow-up endoscopy among dyspeptic patients without abnormal findings on previous endoscopy is unclear. We analyzed the multicenter-collected data from the Korean Society of Neurogastroenterology and Motility. METHODS: We collected clinical data of the patients who visited the gastroenterology department and underwent 2 or more sessions of upper endoscopy during 2012–2017 at 6 university hospitals in Korea. Patients with endoscopic interval between 90 days and 760 days were included. For those with multiple endoscopic sessions, only the first 2 were analyzed. Positive outcome was defined as adenoma or cancer in the upper gastrointestinal tract. To identify the point of change and estimate the properties of the stochastic process before and after the change, we used Bayesian regression with Metropolis-Hastings algorithm. RESULTS: There were 1595 patients. Mean age was 58.8 years (standard deviation, 12.8). Median interval of endoscopy was 437 days (standard deviation, 153). On follow-up endoscopy, there were 12 patients (0.75%) who had neoplasia (4 with gastric cancer and 8 with gastric adnoma). As with the prior hypothesis, we presumed the change point (CP) of increase in frequency of organic lesion as 360 days. After random-walk Metropolis-Hastings sampling with Markov-Chain Monte Carlo iterations of 5000, the CP was 560 days (95% credible interval, 139–724). Estimated average of frequency of dysplastic lesions increased by a factor of 4.4 after the estimated CP. CONCLUSION: To rule out dysplastic lesions among dyspeptic patients who had previously normal endoscopy, a 2-year interval could be offered as follow-up interval for repeat upper endoscopy.
Adenoma
;
Bayes Theorem
;
Dyspepsia
;
Endoscopy
;
Follow-Up Studies
;
Gastroenterology
;
Gastroscopy
;
Hospitals, University
;
Humans
;
Korea
;
Stomach Neoplasms
;
Upper Gastrointestinal Tract
8.Female with 46, XY karyotype.
Eun Jung JUNG ; Do Hwa IM ; Yong Hee PARK ; Jung Mi BYUN ; Young Nam KIM ; Dae Hoon JEONG ; Moon Su SUNG ; Ki Tae KIM ; Hyo Jung AN ; Soo Jin JUNG ; Kyung Bok LEE
Obstetrics & Gynecology Science 2017;60(4):378-382
Disorders of sex development (DSD) are congenital conditions characterized by atypical development of chromosomal, gonadal, and phenotypic sex. 46, XY DSD can result from disorders of testicular development or disorders of androgen synthesis/action. Prophylactic gonadectomy should be considered in patients with 46, XY DSD because of the increased risk of gonadal malignancy. We report two rare cases of 46, XY DSD, including XY pure gonadal dysgenesis and complete androgen insensitivity syndrome, who underwent a prophylactic gonadectomy.
46, XY Disorders of Sex Development
;
Androgen-Insensitivity Syndrome
;
Disorders of Sex Development
;
Female*
;
Gonadal Dysgenesis
;
Gonadal Dysgenesis, 46,XY
;
Gonads
;
Humans
;
Karyotype*
;
Male
9.Rapid Spontaneous Resolution of Acute Subdural Hematoma in a Patient with Liver Cirrhosis.
Hong Ju BAE ; Sang Bok LEE ; Do Sung YOO ; Pil Woo HUH ; Tae Gyu LEE ; Kyoung Suok CHO
Korean Journal of Neurotrauma 2014;10(2):134-136
Acute subdural hematoma (ASDH) constitutes one of the most critical emergencies in neurosurgery and rapid spontaneous resolution of ASDH is an infrequent phenomenon. Several mechanisms have been attributed to explain this phenomenon including redistribution of subdural blood, dilution by cerebral spinal fluid and brain atrophy. Rapid resolution of ASDH related to coagulopathy is a rare phenomenon; to our knowledge, only one case has been reported. We report on a patient who showed rapid resolution of ASDH with coagulopathy and also discuss such a rare case with speculation of the coagulopathy as a factor to promote this phenomenon.
Atrophy
;
Blood Coagulation Disorders
;
Brain
;
Emergencies
;
Hematoma, Subdural, Acute*
;
Humans
;
Liver Cirrhosis*
;
Neurosurgery
10.Endovascular Treatment of the Distal Internal Carotid Artery Large Aneurysm.
Hong Ju BAE ; Do Sung YOO ; Pil Woo HUH ; Tae Gyu LEE ; Kyoung Suok CHO ; Sang Bok LEE
Journal of Cerebrovascular and Endovascular Neurosurgery 2014;16(3):200-208
OBJECTIVE: According to the development of endovascular technique and devices, larger aneurysms on the distal internal carotid artery (ICA) can be treated using a less invasive method. The authors report on clinical and angiographic outcomes of these aneurysms treated using an endovascular technique. MATERIALS AND METHODS: Data on 21 patients with large aneurysms at distal ICA treated by endovascular method between January 2005 and December 2012 were included in this retrospective analysis. RESULTS: Clinical outcome of patients showed strong correlation with the initial neurologic status (p < 0.05). Aneurysm morphology showed saccular, fusiform, and wide-neck in 12, six and three patients. Six patients underwent stent assisted coiling and the other 15 patients underwent simple coiling. Aneurysm occlusion was performed immediately after embolization with near-complete (Raymond class 1-2) in 20 patients (95.2%) and incomplete (Raymond class 3) in one patient (4.8%). Delayed thrombotic occlusion occurred in two patients and their clinical result was fatal. Another five patients died in the hospital, from massive brain edema and/or increased intracranial pressure due to initial subarachnoid hemorrhage. Overall mortality was 30% (seven out of 21). Fatal complication related to the endovascular procedure occurred in two patients with thrombosis at middle cerebral artery (one with stent, the other without it). CONCLUSION: Recent developed endovascular device and technique is safe enough and a less invasive method for distal large or giant aneurysms. Based on our analysis of the study, we suspect that coil embolization of large distal ICA aneurysms (with or without stenting) is effective and safe.
Aneurysm*
;
Brain Edema
;
Carotid Artery, Internal*
;
Embolization, Therapeutic
;
Endovascular Procedures
;
Humans
;
Intracranial Pressure
;
Middle Cerebral Artery
;
Mortality
;
Retrospective Studies
;
Stents
;
Subarachnoid Hemorrhage
;
Thrombosis

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