SH2B1 Defends Against Energy Imbalance, Obesity, and Metabolic Disease via a Paraventricular Hypothalamus→Dorsal Raphe Nucleus Neurocircuit.

SH2B1 mutations are associated with obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in humans. Global deletion of Sh2b1 results in severe obesity, type 2 diabetes, and MASLD in mice. Neuron-specific restoration of SH2B1 rescues the obesity phenotype of Sh2b1-null mice, indicating that the brain is a main SH2B1 target. However, SH2B1 neurocircuits remain elusive. SH2B1-expressing neurons in the paraventricular hypothalamus (PVHSH2B1) and a PVHSH2B1→dorsal raphe nucleus (DRN) neurocircuit are identified here. PVHSH2B1 axons monosynaptically innervate DRN neurons. Optogenetic stimulation of PVHSH2B1 axonal fibers in the DRN suppresses food intake. Chronic inhibition of PVHSH2B1 neurons causes obesity. In male and female mice, either embryonic-onset or adult-onset deletion of Sh2b1 in PVH neurons causes energy imbalance, obesity, insulin resistance, glucose intolerance, and MASLD. Ablation of Sh2b1 in the DRN-projecting PVHSH2B1 subpopulation also causes energy imbalance, obesity, and metabolic disorders. Conversely, SH2B1 overexpression in either total or DRN-projecting PVHSH2B1 neurons protects against diet-induced obesity. SH2B1 binds to TrkB and enhances brain-derived neurotrophic factor (BDNF) signaling. Ablation of Sh2b1 in PVHSH2B1 neurons induces BDNF resistance in the PVH, contributing to obesity. In conclusion, these results unveil a previously unrecognized PVHSH2B1→DRN neurocircuit through which SH2B1 defends against obesity by enhancing BDNF/TrkB signaling.

Dual-Photosensitizer Synergy Empowers Ambient Light Photoactivation of Indium Oxide for High-Performance NO2 Sensing.

Light-activated chemiresistors offer a powerful approach to achieving lower-temperature gas sensing with unprecedented sensitivities. However, an incomplete understanding of how photoexcited charge carriers enhance sensitivity obstructs the rational design of high-performance sensors, impeding the practical utilization under commonly accessible light sources instead of ultraviolet or higher-energy sources. Here, a rational approach is presented to modulate the electronic properties of the parent metal oxide phase, exemplified by this model system of Bi-doped In2O3 nanofibers decorated with Au nanoparticles (NPs) that exhibit superior NO2 sensing performance. Bi doping introduces mid-gap energy levels into In2O3, promoting photoactivation even under visible blue light. Additionally, green-absorbing plasmonic Au NPs facilitate electron transfer across the heterojunction, extending the photoactive region toward the green light. It is revealed that the direct involvement of photogenerated charge carriers in gas adsorption and desorption processes is pivotal for enhancing gas sensing performance. Owing to the synergistic interplay between the Bi dopants and the Au NPs, the Au-BixIn2-xO3 (x = 0.04) sensing layers attain impressive response values (Rg/Ra = 104 at 0.6 ppm NO2) under green light illumination and demonstrate practical viability through evaluation under simulated mixed-light conditions, all of which significantly outperforms previously reported visible light-activated NO2 sensors.

Rapid discrimination of Panax ginseng powder adulterated with various root plants by FT-IR spectroscopy coupled with multivariate analysis.

Panax ginseng powder adulterated with other root plants (arrowroot, bellflower, and lance asiabell) was discriminated using Fourier transform infrared (FT-IR) spectroscopy, combined with multivariate analysis. Principal component analysis visually diagnosed the adulteration by showing two distinct clusters based on presence of adulteration. Wavenumber regions (1000 cm-1 and 3300 cm-1) selected from the loading plot associated with the vibration of OH and CH bond in ginsenoside and aromatic compounds. A quantitative model for the content of ginsenosides and specific aromatic compounds as indicators of pure ginseng powder, was developed based on partial least square regression analysis. The performance of the prediction model preprocessed with the Savizky-Golay 1st derivative was improved to R2 of 0.9650, 0.9635, and 0.9591 for Rb1, Rc, and ß-Panasinsene, respectively. Therefore, FT-IR technology makes it possible to rapidly authenticate pure ginseng product based on the ginsenoside contents and aroma compound.

Cauda equina syndrome by extrusion of lumbar disc after lumbar sympathetic neurolysis.

A 56-year-old woman experienced persistent excruciating pain with peroneal nerve injury in the anterior aspect of the lower leg after knee surgery. In our pain clinic, we diagnosed the patient with complex regional pain syndrome and performed lumbar sympathetic neurolysis (LSN) with absolute alcohol at the 3rd lumbar vertebra (L3). After the next follow-up, she complained of continuous dull low back pain, anal dysregulation, and fecal incontinence. We performed magnetic resonance imaging (MRI) to rule out other existing pathologies of back pain. On MRI, the nucleus pulposus was moderately extruded to the central zone with inferior sequestration at L2/3, and moderate central canal stenosis was observed at L2/3. She underwent partial laminectomy with discectomy at L2 level. We were not sure of the cause of disc herniation, but we strongly suspected that LSN at the L3 vertebral level was related to the pathology. Therefore, we discuss this unusual case.

LepRb+ cell-specific deletion of Slug mitigates obesity and nonalcoholic fatty liver disease in mice.

Leptin exerts its biological actions by activating the long-form leptin receptor (LepRb). LepRb signaling impairment and leptin resistance are believed to cause obesity. The transcription factor Slug - also known as Snai2 - recruits epigenetic modifiers and regulates gene expression by an epigenetic mechanism; however, its epigenetic action has not been explored in leptin resistance. Here, we uncover a proobesity function of neuronal Slug. Hypothalamic Slug was upregulated in obese mice. LepRb+ cell-specific Slug-knockout (SlugΔLepRb) mice were resistant to diet-induced obesity, type 2 diabetes, and liver steatosis and experienced decreased food intake and increased fat thermogenesis. Leptin stimulated hypothalamic Stat3 phosphorylation and weight loss to a markedly higher level in SlugΔLepRb than in Slugfl/fl mice, even before their body weight divergence. Conversely, hypothalamic LepRb+ neuron-specific overexpression of Slug, mediated by AAV-hSyn-DIO-Slug transduction, induced leptin resistance, obesity, and metabolic disorders in mice on a chow diet. At the genomic level, Slug bound to and repressed the LepRb promoter, thereby inhibiting LepRb transcription. Consistently, Slug deficiency decreased methylation of LepRb promoter H3K27, a repressive epigenetic mark, and increased LepRb mRNA levels in the hypothalamus. Collectively, these results unravel what we believe to be a previously unrecognized hypothalamic neuronal Slug/epigenetic reprogramming/leptin resistance axis that promotes energy imbalance, obesity, and metabolic disease.

Anti-Oxidant and Anti-Inflammatory Effects of Astaxanthin on Gastrointestinal Diseases.

A moderate amount of reactive oxygen species (ROS) is produced under normal conditions, where they play an important role in cell signaling and are involved in many aspects of the immune response to pathogens. On the other hand, the excessive production of ROS destructs macromolecules, cell membranes, and DNA, and activates pro-inflammatory signaling pathways, which may lead to various pathologic conditions. Gastrointestinal (GI) mucosa is constantly exposed to ROS due to the presence of bacteria and other infectious pathogens in food, as well as alcohol consumption, smoking, and the use of non-steroidal anti-inflammatory drugs (NSAID). Prolonged excessive oxidative stress and inflammation are two major risk factors for GI disorders such as ulcers and cancers. Bioactive food compounds with potent anti-oxidant and anti-inflammatory activity have been tested in experimental GI disease models to evaluate their therapeutic potential. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid that is naturally present in algae, yeast, salmon, shrimp, and krill. It has been shown that AST exhibits protective effects against GI diseases via multiple mechanisms. Residing at the surface and inside of cell membranes, AST directly neutralizes ROS and lipid peroxyl radicals, enhances the activity of anti-oxidant enzymes, and suppresses pro-inflammatory transcription factors and cytokines. In addition, AST has been shown to inhibit cancer cell growth and metastasis via modulating cell proliferation-related pathways, apoptosis, and autophagy. Considering the potential benefits of AST in GI diseases, this review paper aims to summarize recent advances in AST research, focusing on its anti-oxidant and anti-inflammatory effects against gastric and intestinal ulcers and cancers.

The Effects of Remifentanil and Fentanyl on Emergence Agitation in Pediatric Strabismus Surgery.

Emergence agitation (EA) is one of the main concerns in the field of pediatric anesthesia using sevoflurane. We investigated the effects of remifentanil and fentanyl on the incidence of EA in pediatric patients undergoing strabismus surgery. Ninety children were randomly allocated into two groups and received either remifentanil (group R: intraoperatively remifentanil 0.2 µg/kg/min) or fentanyl (group F: fentanyl 2 µg/kg at anesthetic induction) intraoperatively. After surgery, EA incidence was assessed using a four-point agitation scale and Pediatric Anesthesia Emergence Delirium (PAED) scale in the post-anesthesia care unit. Face, leg, activity, cry, and consolability (FLACC) scores for postoperative pain were also assessed. The incidence of EA using the four-point agitation scale (scores ≥ 3) was similar in both groups (remifentanil group, 28.89% vs. fentanyl group, 24.44%). Similar results were obtained using the PAED scale (scores > 12), with an incidence of 33.33% in the remifentanil group and 26.67% in the fentanyl group. Differences in FLACC scores were not found to be statistically significant. A single bolus administration of fentanyl during anesthetic induction and continuous infusion of remifentanil during surgery had similar effects on the EA incidence in these pediatric patients.

Reverse Takotsubo cardiomyopathy with left bundle branch block after anesthesia induction in a patient with subarachnoid hemorrhage: a case report.

Cardiac dysfunction after subarachnoid hemorrhage (SAH) is described as Takotsubo or reverse Takotsubo cardiomyopathy that shows transient left ventricular wall motion abnormalities with electrocardiogram (ECG) changes. ST change followed by T inversion is a common ECG finding complicated with these disorders, left bundle branch block (LBBB) may be a potential ECG pattern which is seen. In this case, we describe the clinical profile and outcomes of a patient with LBBB and reverse Takotsubo cardiomyopathy after anesthetic induction, which was scheduled as an emergent external ventricular drainage after SAH. This is the first report of an LBBB pattern in reverse Takotsubo cardiomyopathy.

Adapted Physical Education Teachers' Job Satisfaction.

Grounded in occupational socialization theory, the authors examined adapted physical education (APE) teachers' job satisfaction. Twelve (nine female and three male) APE teachers who had 3-43 years of teaching experience participated in the study. A semistructured interview was employed. The interviews focused on the participants' roles and responsibilities. The following questions guided this study: (a) What social agents positively impact APE teachers' job satisfaction? (b) what APE teachers' roles and responsibilities are related to job satisfaction? and (c) what type of working conditions are linked to APE teachers' job satisfaction? Thematic analysis was employed to analyze the data. The following four themes emerged from the analysis: (a) support from administrators, physical education teachers, and colleagues; (b) relevant and meaningful professional development; (c) itinerant working conditions; and (d) seeing students' progress and achievement. The results of this study provide several implications to enhance APE teachers' job satisfaction.

Role of Leptin in the Digestive System.

Leptin is a pluripotent peptide hormone produced mainly by adipocytes, as well as by other tissues such as the stomach. Leptin primarily acts on the central nervous system, particularly the hypothalamus, where this hormone regulates energy homeostasis and neuroendocrine function. Owing to this, disruption of leptin signaling has been linked with numerous pathological conditions. Recent studies have also highlighted the diverse roles of leptin in the digestive system including immune regulation, cell proliferation, tissue healing, and glucose metabolism. Of note, leptin acts differently under physiological and pathological conditions. Here, we review the current knowledge on the functions of leptin and its downstream signaling in the gastrointestinal tract and accessory digestive organs, with an emphasis on its physiological and pathological implications. We also discuss the current therapeutic uses of recombinant leptin, as well as its limitations.

Author Correction: Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease.

Leptin stimulates the sympathetic nervous system (SNS), energy expenditure, and weight loss; however, the underlying molecular mechanism remains elusive. Here, we uncover Sh2b1 in leptin receptor (LepR) neurons as a critical component of a SNS/brown adipose tissue (BAT)/thermogenesis axis. LepR neuron-specific deletion of Sh2b1 abrogates leptin-stimulated sympathetic nerve activation and impairs BAT thermogenic programs, leading to reduced core body temperature and cold intolerance. The adipose SNS degenerates progressively in mutant mice after 8 weeks of age. Adult-onset ablation of Sh2b1 in the mediobasal hypothalamus also impairs the SNS/BAT/thermogenesis axis; conversely, hypothalamic overexpression of human SH2B1 has the opposite effects. Mice with either LepR neuron-specific or adult-onset, hypothalamus-specific ablation of Sh2b1 develop obesity, insulin resistance, and liver steatosis. In contrast, hypothalamic overexpression of SH2B1 protects against high fat diet-induced obesity and metabolic syndromes. Our results unravel an unrecognized LepR neuron Sh2b1/SNS/BAT/thermogenesis axis that combats obesity and metabolic disease.

Deletion of metal transporter Zip14 (Slc39a14) produces skeletal muscle wasting, endotoxemia, Mef2c activation and induction of miR-675 and Hspb7.

Skeletal muscle represents the largest pool of body zinc, however, little is known about muscle zinc homeostasis or muscle-specific zinc functions. Zip14 (Slc39a14) was the most highly expressed zinc transporter in skeletal muscle of mice in response to LPS-induced inflammation. We compared metabolic parameters of skeletal muscle from global Zip14 knockout (KO) and wild-type mice (WT). At basal steady state Zip14 KO mice exhibited a phenotype that included muscle wasting and metabolic endotoxemia. Microarray and qPCR analysis of gastrocnemius muscle RNA revealed that ablation of Zip14 produced increased muscle p-Mef2c, Hspb7 and miR-675-5p expression and increased p38 activation. ChIP assays showed enhanced binding of NF-[Formula: see text] to the Mef2c promoter. In contrast, LPS-induced systemic inflammation enhanced Zip14-dependent zinc uptake by muscle, increased expression of Atrogin1 and MuRF1 and markedly reduced MyoD. These signatures of muscle atrophy and cachexia were not influenced by Zip14 ablation, however. LPS-induced miR-675-3p and -5p expression was Zip14-dependent. Collectively, these results with an integrative model are consistent with a Zip14 function in skeletal muscle at steady state that supports myogenesis through suppression of metabolic endotoxemia and that Zip14 ablation coincides with sustained activity of phosphorylated components of signaling pathways including p-Mef2c, which causes Hspb7-dependent muscle wasting.

Surgical Management of Sigmoid Volvulus: A Multicenter Observational Study.

PURPOSE: This study aimed to evaluate real-world clinical outcomes from surgically treated patients for sigmoid volvulus. METHODS: Five tertiary centers participated in this retrospective study with data collected from October 2003 through September 2018, including demographic information, preoperative clinical data, and information on laparoscopic/open and elective/emergency procedures. Outcome measurements included operation time, postoperative hospitalization, and postoperative morbidity. RESULTS: Among 74 patients, sigmoidectomy was the most common procedure (n = 46), followed by Hartmann's procedure (n = 23), and subtotal colectomy (n = 5). Emergency surgery was performed in 35 cases (47.3%). Of the 35 emergency patients, 34 cases (97.1%) underwent open surgery, and a stoma was established for 26 patients (74.3%). Elective surgery was performed in 39 cases (52.7%), including 21 open procedures (53.8%), and 18 laparoscopic surgeries (46.2%). Median laparoscopic operation time was 180 minutes, while median open surgery time was 130 minutes (P < 0.001). Median postoperative hospitalization was 11 days for laparoscopy and 12 days for open surgery. There were 20 postoperative complications (27.0%), and all were resolved with conservative management. Emergency surgery cases had a higher complication rate than elective surgery cases (40.0% vs. 15.4%, P = 0.034). CONCLUSION: Relative to elective surgery, emergency surgery had a higher rate of postoperative complications, open surgery, and stoma formation. As such, elective laparoscopic surgery after successful sigmoidoscopic decompression may be the optimal clinical option.

Effects of an Internet-based informational video on preoperative anxiety in patients with colorectal cancer.

PURPOSE: Surgery is the primary curative treatment for colorectal cancer; however, it remains a frightening procedure that can cause stress and pain in affected patients. Therefore, patients typically experience significant anxiety during the preoperative period, which has been associated with poorer outcome after surgery. This study aimed to evaluate the effect of an Internet-based informational video on preoperative anxiety level in patients with colorectal cancer. METHODS: This prospective, single-arm, observational study included patients scheduled to undergo elective colorectal cancer surgery, who did not have a history of previous surgery or major cognitive impairment. The primary outcome measure was the change in Amsterdam Preoperative Anxiety and Information Scale - Anxiety (APAIS-A) before and after watching a 5-min informational video (https://youtu.be/VzhtOMPUe4Q) during the preoperative period. Secondary outcome measures were the change in Hospital Anxiety and Depression Scale (HADS), length of postoperative hospital day, and postoperative morbidity. RESULTS: Thirty-two patients were enrolled. Anxiety was significantly decreased after watching the video (APAIS-A score: from 10.8 ± 3.7 to 8.2 ± 3.2, P < 0.001, mean reduction: 22.2%). HADS score was also significantly decreased (from 5.8 ± 4.4 to 4.0 ± 3.3, P = 0.001, mean reduction: 26.5%). All preoperative anxiety level did not significantly differ between patients who developed postoperative complication and those who did not. CONCLUSION: The informational video was an effective tool to reduce preoperative anxiety. Viewing this video may confer a higher level of confidence and realistic expectations, as well as reducing patients' preoperative anxiety.

Discrepancy of Medical Terminology Regarding Colorectal Surgery Between South and North Korea.

PURPOSE: We aimed to investigate the extent of heterogeneity in medical terminology between South and North Korea by comparing medical terms related to the colorectal system. METHODS: North Korean medical terms were collected from the sections on diseases of the small intestine and colon in a surgery textbook from North Korea, and those terms were compared with their corresponding terms in a South Korean medical terminology textbook. The terms were categorized as either identical, similar, showing disparity, or not used in South Korea. In a subsection analysis, the terms were allocated to pathophysiology, diagnosis, symptoms and examination, drugs, testing, treatment, or others according to the categorization used in the textbook. RESULTS: We found 705 terms in the North Korean textbook, most of which were pathophysiological terms (206, 29.2%), followed by diagnostic terms (165, 23.4%) and symptom and examination terms (122, 17.3%). Treatment-, drug-, and testing-related terms constituted 15.5%, 5.8%, and 4.1% of the 705 terms, respectively. There were 331 identical terms (47.0%) and 146 similar terms (20.7%); 126 terms (17.9%) showed disparity. Another 102 terms (14.5%) were not used in South Korea. The pathophysiological terms were the least heterogeneous, with 61.2% being identical terms used in both countries. However, 26.8% of the terms in the drug category were not used in South Korea. CONCLUSION: The present study showed that less than 50% of the terms for the colorectal system used in South and North Korea were identical. As the division between South and North Korea persists, the heterogeneity of medical terminology is expected to increase.

ß-Carotene Inhibits Activation of NF-κB, Activator Protein-1, and STAT3 and Regulates Abnormal Expression of Some Adipokines in 3T3-L1 Adipocytes.

BACKGROUND: Oxidative stress occurs in white adipose tissue and dysregulates the expression of adipokines secreted from adipocytes. Since adipokines influence inflammation, supplementation with antioxidants might be beneficial for preventing oxidative stress-mediated inflammation in adipocytes and inflammation-associated complications. ß-Carotene is the most prominent antioxidant carotenoid and scavenges reactive oxygen species in various tissues. The purpose of this study was to determine whether ß-carotene regulates the expression of adipokines, such as adiponectin, monocyte chemoattractant protein-1 (MCP-1), and regulated on activation, normal T cell expressed and secreted (RANTES) in 3T3-L1 adipocytes treated with glucose/glucose oxidase (G/GO). METHODS: 3T3-L1 adipocytes were cultured with or without ß-carotene and treated with G/GO, which produces H2O2. mRNA and protein levels in the medium were determined by a real-time PCR and an ELISA. DNA binding activities of transcription factors were assessed using an electrophoretic mobility shift assay. RESULTS: G/GO treatment increased DNA binding affinities of redox-sensitive transcription factors, such as NF-κB, activator protein-1 (AP-1), and STAT3. G/GO treatment reduced the expression of adiponectin and increased the expression of MCP-1 and RANTES. G/GO-induced activations of NF-κB, AP-1, and STAT3 were inhibited by ß-carotene. G/GO-induced dysregulation of adiponectin, MCP-1, and RANTES were significantly recovered by treatment with ß-carotene. CONCLUSIONS: ß-Carotene inhibits oxidative stress-induced inflammation by suppressing pro-inflammatory adipokines MCP-1 and RANTES, and by enhancing adiponectin in adipocytes. ß-Carotene may be beneficial for preventing oxidative stress-mediated inflammation, which is related to adipokine dysfunction.

Discrepancies in general surgery medical terminology between South and North Korea.

PURPOSE: The purpose of this study was to categorize surgery-related medical terminologies used in South and North Korea and to compare and analyze discrepancies observed in the terms. METHODS: This study collected medical terminology used in the North Korean medical book "Surgery" and compared it to medical terminology found in the medical glossary of South Korea. The order of the subtitle was described according to the Instruction to Authors. RESULTS: In total, there were 2,168 individual medical terms, of which only 1,004 words (46.3%) were identical to South Korean medical terms. There were 581 similar terms (26.8%), 265 different terms (12.2%), and 318 terms that are nonexistent in South Korea (14.7%). CONCLUSION: Less than half of the medical terms used in North Korea match those used in South Korea. It is expected that the prolongation of the current division of South and North Korea will only worsen this discrepancy. Further efforts to bridge the gap through academic exchange between South Korea and North Korea are required in preparation for an era of reunification.

Heat Tolerance Induction of the Indian Meal Moth (Lepidoptera: Pyralidae) Is Accompanied by Upregulation of Heat Shock Proteins and Polyols.

The Indian meal moth, Plodia interpunctella, causes massive damage to stored grains and processed foods. Heat treatment has been widely used to control insect pests infesting stored grains. However, heat treatment may result in unsatisfactory control owing to heat tolerance of target insects. This study quantified the heat tolerance and analyzed its induction in P. interpunctella. Susceptibility of P. interpunctella to different high temperatures was assessed in all developmental stages. Heat treatment at 44 °C for 1 h caused significant mortalities to all developmental stages, with late-instar larvae exhibiting the highest tolerance. However, the survivorship to heat treatment was significantly increased by pre-exposure to 37 °C for 30 min. The induction of heat tolerance was accompanied by upregulation of two heat shock proteins of Hsc70 and Hsp90. Trehalose and glycerol concentrations in the hemolymph also increased after pre-exposure to 37 °C for 30 min. RNA interference (RNAi) by specific double-stranded RNAs effectively suppressed the inducible expressions of both Hsc70 and Hsp90 in response to 37 °C for 30 min. Either RNAi of Hsc70 or Hsp90 significantly impaired the heat tolerance induction of P. interpunctella. These results suggest that the induction of heat tolerance in P. interpunctella involves the upregulation of these heat shock proteins and hemolymph polyol levels.

Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress.

Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet-induced ER stress using Zip14-/- (KO) mice, which exhibit impaired hepatic zinc uptake. Here, we report that ZIP14-mediated hepatic zinc uptake is critical for adaptation to ER stress, preventing sustained apoptosis and steatosis. Impaired hepatic zinc uptake in Zip14 KO mice during ER stress coincides with greater expression of proapoptotic proteins. ER stress-induced Zip14 KO mice show greater levels of hepatic steatosis due to higher expression of genes involved in de novo fatty acid synthesis, which are suppressed in ER stress-induced WT mice. During ER stress, the UPR-activated transcription factors ATF4 and ATF6α transcriptionally up-regulate Zip14 expression. We propose ZIP14 mediates zinc transport into hepatocytes to inhibit protein-tyrosine phosphatase 1B (PTP1B) activity, which acts to suppress apoptosis and steatosis associated with hepatic ER stress. Zip14 KO mice showed greater hepatic PTP1B activity during ER stress. These results show the importance of zinc trafficking and functional ZIP14 transporter activity for adaptation to ER stress associated with chronic metabolic disorders.