Increased Suicide Mortality and Reduced Life Expectancy Associated With Ambient Heat Exposure.

INTRODUCTION: Ambient heat exposure is a risk factor for suicide in many regions of the world. However, little is known about the extent to which life expectancy has been shortened by heat-related suicide deaths. This study aimed to evaluate the short-term effects of heat on suicide mortality and quantify the reduced life expectancy associated with heat in China. METHODS: A time-stratified, case-crossover analysis in 2023 was performed during the warm season (May to September) from 2016 to 2020 to assess the short-term association between extreme heat (the 95th percentile of mean temperature) and suicide mortality in Anhui Province, China. A subgroup analysis was performed according to sex, age, marital status, suicide type, and region. The attributable fraction and years of life lost due to heat were calculated, and the heat-related life expectancy loss was estimated. RESULTS: This study included 9,642 suicide deaths, with an average age of 62.4 years and 58.8% of suicides in males. Suicide risk was associated with an 80.7% increase (95% confidence interval [CI]: 21.4%-68.9%) after exposure to extreme heat (30.6°C) in comparison to daily minimum temperature (7.9°C). Subgroup analysis revealed that heat-related suicide risk was more prominent in the married population than in the unmarried population. Heat was estimated to be associated with 31.7% (95% CI: 18.0%-43.2%) of the suicides, corresponding to 7.0 years of loss in life expectancy for each decedent. CONCLUSIONS: Heat exposure was associated with an increased risk of suicide and reduced life expectancy. However, further prospective studies are required to confirm this relationship.

METTL3 promotes m6A hypermethylation of RBM14 via YTHDF1 leading to the progression of hepatocellular carcinoma.

Liver is a well-known immunological organ with unique microenvironment. In normal conditions, the rich immune-infiltrating cells cooperate with non-parenchymal cells, such as Kupffer cells (KCs). The presence of liver immunosuppressive microenvironment underlines the importance to dissect this interaction to understand how this cross-talk promotes tumor growth in hepatocellular carcinoma (HCC). Therefore, the aim of the study here was to probe the role of methyltransferase-like 3 (METTL3) in the HCC progression and its effect on the polarization of KCs. KCs showed M2 polarization, and METTL3 was overexpressed in our collected HCC tissues relative to adjacent tissues. METTL3 depletion inhibited the M2 polarization of KCs, thereby reverting the malignant phenotype of HCC cells in vitro and growth and metastasis in vivo. Mechanistically, YTH domain-containing family protein 1 (YTHDF1) bound to RNA-binding protein 14 (RBM14), whereas METTL3 knockdown in KCs cells suppressed RBM14 expression by decreasing N-methyladenosine (m6A) methylation. Overexpression of RBM14 mitigated the anti-tumor effects of sh-METTL3 in vitro and in vivo. It is suggested that the mechanism of sh-METTL3 suppressing the polarization of KCs and the progression of HCC is to regulate the RBM14 expression via YTHDF1-dependent m6A modification.

Histone deacetylase 2 regulates STAT1-dependent upregulation of atypical chemokine receptor 3 to induce M2 macrophage migration and immune escape in hepatocellular carcinoma.

Atypical chemokine receptor 3 (ACKR3) has been linked to the tumor microenvironment. This work investigates the effects of ACKR3 and its regulatory molecules on the chemotactic migration of tumor-associated macrophages (TAMs) in hepatocellular carcinoma (HCC). RT-qPCR and western blot assays identified elevated ACKR3 and HDAC2 levels in HCC tissues and cells. Knockdown or overexpression of ACKR3 was induced in HCC cells through vectors of lentivirus plasmids, and then the conditioned medium of the HCC cells was collected to stimulate TAMs. The stimulated TAMs were co-cultured with CD3+ T cells. ACKR3 knockdown in HCC cells inhibited migration of TAMs and promoted M1 polarization, which restored the activity of T cells. Histone deacetylase 2 (HDAC2) recruited signal transducer and activator of transcription 1 (STAT1) to the ACKR3 promoter to activate ACKR3 transcription. HDAC2 silencing suppressed nuclear translocation of STAT1 and decreased ACKR3 expression. HDAC2 knockdown in HCC cells similarly suppressed TAM migration, promoted M1 polarization, and restored T cell function, but these changes were inversed by ACKR3 upregulation. HDAC2 or ACKR3 silencing weakened tumor growth and immune escape in mice. In conclusion, this study demonstrates that HDAC2 upregulates ACKR3 via STAT1 to induce migration of M2 macrophages and immune escape in HCC.

Factors correlated with targeted prevention for prediabetes classified by impaired fasting glucose, impaired glucose tolerance, and elevated HbA1c: A population-based longitudinal study.

Background: There is still controversy surrounding the precise characterization of prediabetic population. We aim to identify and examine factors of demographic, behavioral, clinical, and biochemical characteristics, and obesity indicators (anthropometric characteristics and anthropometric prediction equation) for prediabetes according to different definition criteria of the American Diabetes Association (ADA) in the Chinese population. Methods: A longitudinal study consisted of baseline survey and two follow-ups was conducted, and a pooled data were analyzed. Prediabetes was defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or elevated glycosylated hemoglobin (HbA1c) according to the ADA criteria. Robust generalized estimating equation models were used. Results: A total of 5,713 (58.42%) observations were prediabetes (IGT, 38.07%; IGT, 26.51%; elevated HbA1c, 23.45%); 9.66% prediabetes fulfilled all the three ADA criteria. Among demographic characteristics, higher age was more evident in elevated HbA1c [adjusted OR (aOR)=2.85]. Female individuals were less likely to have IFG (aOR=0.70) and more likely to suffer from IGT than male individuals (aOR=1.41). Several inconsistency correlations of biochemical characteristics and obesity indicators were detected by prediabetes criteria. Body adiposity estimator exhibited strong association with prediabetes (D10: aOR=4.05). For IFG and elevated HbA1c, the odds of predicted lean body mass exceed other indicators (D10: aOR=3.34; aOR=3.64). For IGT, predicted percent fat presented the highest odds (D10: aOR=6.58). Conclusion: Some correlated factors of prediabetes under different criteria differed, and obesity indicators were easily measured for target identification. Our findings could be used for targeted intervention to optimize preventions to mitigate the obviously increased prevalence of diabetes.

Association of sleep duration and sleep quality with the risk of metabolic syndrome in adults: a systematic review and meta-analysis.

INTRODUCTION: The association between sleep duration and metabolic syndrome (MetS) remains controversial, and few have considered the effects of sleep quality. We performed a meta-analysis to clarify the relationship of sleep duration and sleep quality with the risk of MetS. MATERIAL AND METHODS: We conducted a systematic and comprehensive literature search of electronic databases from inception to 17 February 2022. The effect sizes of covariates from each study were pooled using a random or fixed model, and a restricted cubic spline random-effects meta-analysis was performed to examine the dose-response relationship between sleep duration and MetS. RESULTS: A total of 62 studies were included in this meta-analysis. Compared to normal sleep duration, short sleep duration [odds ratio (OR) = 1.14, 95% confidence interval (CI): 1.10-1.19] and long sleep duration (OR = 1.15, 95% CI: 1.09-1.23) were associated with an increased risk of MetS. The restricted cubic spline analysis indicated that sleep durations of 8.5 h (OR = 0.95, 95% CI: 0.92-0.97) and 11 h (OR = 1.58, 95% CI: 1.31-1.91) were significantly associated with the risk of MetS. The pooled results showed that poor sleep quality (OR = 1.46, 95% CI: 1.03-2.06) and sleep complaints had significant positive associations with MetS. CONCLUSION: Our results demonstrated that short sleep duration increased the risk of developing MetS. Long sleep duration was also associated with MetS, especially for 11 h. 8.5 h can be considered the recommended sleep duration for MetS. Poor sleep quality and sleep complaints were also associated with MetS.

Hypoxia, a key factor in the immune microenvironment.

The physical and chemical pressures in the tumor microenvironment (TME) play an important role in tumor development by regulating stromal elements, including immune cells. Hypoxia can induce a cascade of events in tumor initiation and development via immune regulation. As a dangerous factor, hypoxia activates multiple signaling pathways to reshape the immune microenvironment, leading to immunosuppression. Consequently, targeting hypoxia in the TME is a potential strategy to prevent immune escape and inhibit malignant tumor progression. In this review, we summarized the role of hypoxia-induced factors in the tumor immune escape process and provide a novel pathway to restrain tumor progression and development.

ALDH2 Hampers Immune Escape in Liver Hepatocellular Carcinoma through ROS/Nrf2-mediated Autophagy.

Aldehyde dehydrogenase 2 (ALDH2) has been implicated in the progression of liver hepatocellular carcinoma (LIHC). The most important feature of LIHC is the immune escape process. This study sets to study the role of ALDH2 in regulating immune escape in LIHC. Bioinformatics analysis was applied to examine the expression of ALDH2 in LIHC and its impact on patients' survival. The effect of ALDH2 expression on malignant phenotype of LIHC cells was assessed by gain-of-function assays. RT-qPCR and Western blot were conducted to examine the expression of related factors, thus investigating the downstream mechanisms of ALDH2. ELISA assay was carried out to measure the level of oxidative stress in cells, and crystal violet staining was conducted to observe the killing effect of T cells on tumor cells. Finally, xenograft assay was carried out to verify the role of ALDH2 in vivo.ALDH2 was poorly expressed in LIHC, which predicted dismal prognoses for patients. ALDH2 inhibited the malignant aggressiveness of LIHC cells. ALDH2 blocked the activation of Nrf2 by suppressing reactive oxygen species (ROS) in LIHC, and Nrf2 significantly reversed the tumor-suppressing properties of ALDH2. Nrf2 hindered autophagy and led to immune escape of LIHC cells. Moreover, ALDH2 considerably suppressed the growth of xenografts, increased autophagy and promoted the accumulation of T cells in tumors. In contrast, Nrf2 drastically reversed the repressive effect of ALDH2 on tumor growth.ALDH2 impaired the ROS/Nrf2 axis to promote autophagy, thereby repressing immune escape in LIHC.

Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour.

Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A-D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC50 values of 2.61, 1.19, and 1.74 µM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 µg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC50 of 20.06 µM) and α-glycosidase inhibitor (IC50 of 17.18 µM), while tabernamine, ervahanine B, and ervadivaricatine B only showed α-glycosidase inhibitory activities with IC50 values in the range of 0.95-4.61 µM.

Oncogenic E3 ubiquitin ligase NEDD4 binds to KLF8 and regulates the microRNA-132/NRF2 axis in bladder cancer.

The neuronally expressed developmentally downregulated 4 (NEDD4) gene encodes a ubiquitin ligase that targets the epithelial sodium channel for degradation and has been implicated in tumor growth in various cancers. Hence, in this study, we intended to characterize the functional relevance of the NEDD4-mediated Kruppel-like factor 8/microRNA-132/nuclear factor E2-related factor 2 (KLF8/miR-132/NRF2) axis in the development of bladder cancer. NEDD4 and KLF8 were overexpressed in bladder cancer tissues and were associated with poorer patient survival rates. In bladder cancer cells, NEDD4 intensified the stability and transcriptional activity of KLF8 through ubiquitination to augment cell viability and migratory ability. Our investigations revealed that NEDD4 promotes the binding of KLF8 to the miR-132 promoter region and inhibits the expression of miR-132. KLF8 inhibited the expression of miR-132 to augment the viability and migratory ability of bladder cancer cells. Furthermore, miR-132 downregulated the expression of NRF2 to restrict the viability and migratory ability of bladder cancer cells. In addition, in vivo findings verified that NEDD4 regulates the KLF8/miR-132/NRF2 axis by accelerating tumor growth and lung metastasis. In conclusion, this study highlights NEDD4 as a potential therapeutic target against tumor recurrence and metastasis in bladder cancer.

Effect of Metabolic Health and Obesity Phenotype on Risk of Diabetes Mellitus: A Population-Based Longitudinal Study.

BACKGROUND: Epidemiologic evidence on body mass index (BMI)-metabolic status phenotypes and diabetes risk remains controversial, especially for metabolically healthy obesity (MHO). We aimed to examine the effect of metabolic health and obesity phenotype on diabetes risk in the Chinese population. METHODS: A population-based cohort study was carried out. The baseline survey was conducted in 2017, with two follow-up visits in 2018 and 2020. Diabetes was defined based on the criteria of the World Health Organization. Robust generalized estimating equation models with a binary distribution using a log link and exchange structure were applied for the pooled analysis sample. RESULTS: A total sample of 9623 observations was pooled for the longitudinal data analysis. The average follow-up time was 1.64 years per person and the overall incidence density of diabetes was 6.94% person-years. Decreased diabetes risk was found in metabolically healthy overweight phenotype (RR = 0.65; 95% CI = 0.47-0.90) and no significant associations were detected for the MHO individuals (RR = 0.99; 95% CI = 0.63-1.53) compared with those of metabolically healthy normal weight, in contrast to metabolically unhealthy normal weight (MU-NW) (RR = 1.81; 95% CI = 1.28-2.55), metabolically unhealthy overweight (MU-OW) (RR = 2.02; 95% CI = 1.57-2.61) and metabolically unhealthy obesity (MUO) (RR = 2.48; 95% CI = 1.89-3.26) phenotypes. Significant associations between BMI-metabolic status phenotypes and diabetes were found in both males and females. CONCLUSION: The MUO phenotype needs to be accorded much more importance. MU-NW and MU-OW are also important component for targeted prevention. Our findings can be targeted for optimizing preventive strategies to mitigate the obviously increased prevalence of diabetes.

Protective Effects of Bariatric Surgery on Kidney Functions by Inhibiting Oxidative Stress Responses Through Activating PPARα in Rats With Diabetes.

OBJECTIVE: The aim of this study was to explore the protective effects and the regulatory mechanisms of bariatric surgery on kidney injury in diabetic rats. METHODS: We established a useful type 2 diabetic rat model using high-fat and high-sugar diet feeding following low-dose streptozotocin (STZ) treatment. Sprague-Dawley (SD) rats were randomly divided into the following groups: control (Con) group, diabetic nephropathy (DN) group, and duodenal-jejunal bypass (DJB) surgery group. The food intake and body weight of rats were monitored and the glucose tolerance test (OGTT) test was performed every 2 weeks. The glomerular filtration rate (GFR) and urinary albumin excretion rate (UAFR) were measured to assess renal function. Hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), and Masson staining were used to evaluate renal histopathological changes. TUNEL assay was performed to detect cell apoptosis. The expressions of oxidative stress factors and inflammatory factors in the renal tissues of rats were detected by ELISA. The expressions of PPARα, reactive oxygen species (ROS), and NF-κB were detected by immunofluorescence. For in vitro experiment, HK2 cells cultured with high glucose were treated with PPARα agonist, PPARα antagonist, and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) agonist. The expressions of AMPK/PPARα/NF-κB signaling pathway-related proteins were detected by Western blot. RESULTS: Bariatric surgery improved the glucose tolerance of DN rats. The GFR was decreased, the promotion of urinary albumin excretion rate (UAER) was inhibited, and the renal injury was alleviated. The extracellular matrix fraction was decreased and the renal function was improved. Meanwhile, bariatric surgery activates PPARα, inhibits ROS release, reduces oxidative stress injury, and reduces renal cell apoptosis. In vitro experiment results showed that the AMPK activator could activate PPARα, downregulate NF-κB, and inhibit inflammatory response. The phosphorylation of AMPK was inhibited by PPARα antagonism. CONCLUSION: Bariatric surgery can activate PPARα, inhibit oxidative stress injury, and improve glucose metabolism and renal function in DN rats.

OCT3/4 enhances tumor immune response by upregulating the TET1-dependent NRF2/MDM2 axis in bladder cancer.

This study aimed to investigate the function of OCT3/4 on tumor immune escape in bladder cancer. Initially, the expression of OCT3/4, TET1, NRF2 and MDM2 was quantified in tumor tissues and cells, followed by gain- or loss-of-function studies to define their roles in cell migration, invasion and apoptosis and tumorigenicity in nude mice. Bladder cancer presented with abundant expression levels of OCT3/4, TET1, NRF2 and MDM2. We found that OCT3/4 promoted TET1 expression via binding to its promoter and that TET1 recruited MLL protein to NRF2 promoter and upregulated its expression, while NRF2 enhanced MDM2 expression. Upregulated MDM2 accelerated tumor immune escape in bladder cancer in mice. OCT3/4 knockdown suppressed the cell migration and invasion while inducing apoptosis, and consequently prevented tumor growth and immune escape in mice. Collectively, OCT3/4 may promote the progression of tumor immune escape in bladder cancer through acting as a promoter of the TET1/NRF2/MDM2 axis.

A genetic analysis identifies haplotype at adiponectin locus: Association with the metabolic health and obesity phenotypes.

BACKGROUND: Obesity and metabolic syndrome frequently co-exist and define obese individuals into different obesity phenotypes, such as metabolically healthy obese (MHO), metabolically unhealthy obese (MUO) and metabolically unhealthy normal weight (MUNW). Growing evidence suggests that genetic predisposition and environmental factors can explain the heterogeneity among these phenotypes. METHODS: We conducted a case-control study including 130 MHO, 251 MUNW, 208 MUO and 336 health controls by genotyping 2 SNPs (rs2241766, rs1501299) in ADIPOQ to investigate possible associations between SNPs in the ADIPOQ gene with susceptibility to three obese phenotypes respectively in Chinese Han population. Unconditional logistic regressions were used to detect the association between ADIPOQ SNPs and MHO/MUNW/MUO risks. RESULTS: Variant G allele of rs2241766 was associated with a reduced odds of MUO (additive model: Adjusted OR = 0.55; 95% CI = 0.40-0.75; P < 0.001) and no evidence of any significant association between rs2241766 and MHO phenotype (additive model: Adjusted OR = 0.84; 95% CI = 0.61-1.16; P = 0.306) or MUNW phenotype (additive model: Adjusted OR = 0.95; 95% CI = 0.73-1.24; P = 0.720) was found. Minor allele T of rs1501299 were significantly associated with decreased risk of MHO (Adjusted OR = 0.53; 95% CI = 0.37-0.76; P < 0.001) and MUNW (Adjusted OR = 0.63; 95% CI = 0.48-0.83; P = 0.001) in additive genetic model after correction for multiple testing. CONCLUSIONS: The variant G allele of rs2241766 was negatively associated with risk of MUO and variant T allele of rs1501299 exhibited reduced odds for MHO and MUNW. Beyond that, future studies are warranted to validate and extend our findings.

An association between body image dissatisfaction and digit ratio among Chinese children and adolescents.

Body image dissatisfaction (BID) is a negative evaluation of personal physical characteristics, including dissatisfaction with body shape, gender, sexual organs, appearance and so forth, and it plays an important role in growth and development. The second-to-fourth digit ratio (2D:4D) is recognized as a putative indicator of intra-uterine testosterone to estrogen ratio exposure, and it has been observed that higher levels of fetal testosterone exposure are associated with a lower 2D:4D. The present paper contributes to a better understanding of the biological underpinnings of BID by analyzing BID and the digit ratio (2D:4D). We found that the 2D:4D was positively related to appearance dissatisfaction in boys with first spermatorrhea, which means that low prenatal androgen exposure may increase boys' dissatisfaction with their appearance. In girls with breast development being lower than Tanner stage II, their 2D:4D was negatively related to their body shape dissatisfaction, which means that high prenatal androgen exposure may increase girls' dissatisfaction with their body shape. These results suggest that the prenatal androgen exposure level might play an important role in the body image dissatisfaction of the offspring.

Adiponectin/SIRT1 Axis Induces White Adipose Browning After Vertical Sleeve Gastrectomy of Obese Rats with Type 2 Diabetes.

PURPOSE: White adipose tissue (WAT) browning plays a crucial role in energy metabolism. However, it remains unclear whether WAT browning is involved in the adipose reduction following sleeve gastrectomy (SG). Adiponectin is upregulated after Roux-en-Y gastric bypass surgery. The role of adiponectin in SG was further investigated in the current study. MATERIALS AND METHODS: Diabetic Sprague Dawley rats were randomly divided into control, sham + libitum, sham + food restriction, and sleeve groups. Browning markers, including uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor (PPAR) γ, and PPARγ coactivator-1 alpha (PGC-1α), were examined 4 weeks after the operation. RESULTS: UCP1, PPARγ, and PGC-1α expression were significantly higher in the sleeve group compared to the other study groups. The adipose tissue of the sleeve group exhibited tissue weight loss and additional morphological browning features. In addition, adiponectin expression in the sleeve group was significantly increased. Adiponectin upregulated the expression of the browning genes and sirtuin 1 (SIRT1) in 3T3-L1 adipocytes. SIRT1 could increase the WAT browning levels, revealing that adiponectin induced the browning process via the upregulation of SIRT1. Furthermore, SIRT1 represented a positive regulatory feedback loop for adiponectin. SIRT1 activated adenosine monophosphate-activated protein kinase (AMPK), which can mediate WAT browning. Inhibition of the AMPK signaling pathway by dorsomorphin decreased UCP1, PPARγ, and PGC-1α expression. However, additional studies are needed to understand the relationship between adiponectin and glucose homeostasis. CONCLUSIONS: Sleeve gastrectomy increased adiponectin levels, which in turn upregulated SIRT1. Thus, SIRT1 may function as an endocrine signal to mediate WAT browning.

A Novel Indicator Of Lipid Accumulation Product Associated With Metabolic Syndrome In Chinese Children And Adolescents.

BACKGROUND: The lipid accumulation product (LAP) is a powerful marker for predicting metabolic syndrome (MS) in adults. The present study aimed to propose a novel indicator, the children's lipid accumulation product (CLAP), and to assess its association with MS among Chinese children and adolescents. METHODS: A total of 683 Chinese children aged 8-15 years were recruited using a stratified cluster sampling method in this cross-sectional study. The presence of MS was defined according to the NCEP-ATP III criteria. The effects of BMI, WHtR and the CLAP for predicting MS were compared using logistic regression models and receiver operating characteristic (ROC) curves. RESULTS: The prevalence of MS was 5.1% (6.6% and 3.5% among boys and girls, respectively). Overall obesity (based on BMI), abdominal obesity (based on WHtR) and CLAP≥P75 were significantly associated with an increased risk of MS (ORs (95% CIs) were 143.79 (18.78-1101.22), 86.83 (27.19-277.27), 150.75 (20.11-1130.19), respectively). The area under the ROC curve (AUC) for the CLAP was higher than that for BMI and WHtR for predicting MS, with AUC (95% CI) values of 0.944 (0.913-0.975), 0.895 (0.864-0.927), and 0.928 (0.903-0.953), respectively. CONCLUSION: The children's lipid accumulation product (CLAP) was an effective indicator associated with MS in Chinese children and adolescents and was better than BMI and WHtR for predicting MS.

Hypothalamic nesfatin-1 mediates feeding behavior via MC3/4R-ERK signaling pathway after weight loss in obese Sprague-Dawley rats.

Nesfatin-1 is an anorexic peptide derived from nucleobindin 2 (NUCB2). An increase in hypothalamic nesfatin-1 inhibits feeding behavior and promotes weight loss. However, the effects of weight loss on hypothalamic nesfatin-1 levels are unclear. In this study, obese rats lost weight in three ways: Calorie Restriction diet (CRD), Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). We found an increase in nesfatin-1 serum and cerebrospinal fluid levels after weight loss in obese Sprague-Dawley (SD) rats. Moreover, weight loss also increased hypothalamic melanocortin 3/4 receptor (MC3/4R) and extracellular regulated kinase phosphorylation (p-ERK) signaling. Third ventricle administration of antisense morpholino oligonucleotide (MON) against the gene encoding NUCB2 inhibited hypothalamic nesfatin-1 and p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. Third ventricle administration of SHU9119 (MC3/4R blocker) blocked hypothalamic MC3/4R, inhibited p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. These findings indicate that weight loss leads to an increase in hypothalamic nesfatin-1. The increase in hypothalamic nesfatin-1 participates in regulating feeding behavior through the MC3/4R-ERK signaling especially after SG and RYGB.

Bariatric Surgery in Rats Upregulates FSP27 Expression in Fat Tissue to Affect Fat Hydrolysis and Metabolism.

PURPOSE: To explore the changes in FSP27 expression and fat metabolism in adipose tissue and their relationship after bariatric surgery in rats. METHOD: Food intake, body weight, triglyceride content, fat distribution, and fat cell morphology were evaluated in rats grouped into control, sham, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) groups. Immunohistochemistry and western blotting were used to detect protein expression and real-time PCR was used to detect mRNA expression. Mouse 3T3-L1 preadipocytes were used to assess the effects of different energy levels and nutrient factors on FSP27 in adipocytes. RESULT: Food intake, body weight, and triglyceride levels were reduced in RYGB and SG rats within 28 days after surgery, with a more pronounced effect in the RYGB group. Weight loss was mainly due to loss of fat mass rather than loss of lean mass, with the most pronounced decrease in trunk fat. FSP27 expression increased in lean rat adipocytes accompanied by increased lipid droplets (LDs). In SG and RYGB rats, the FSP27 protein concentration gradually increased in white adipose tissue (WAT) after operation. Hormone-sensitive lipase (HSL), p-HSL/HSL, Adipose Triglyceride Lipase (ATGL), and Comparative Gene Identification-58 (CGI-58) gradually decreased in SG and RYGB rats, but they were always higher than in control and sham animals. FSP27 was also decreased in 3T3-L1 adipocytes of animals with a high-energy diet. CONCLUSION: FSP27 is associated with rat lipid metabolism and its expression varies with energy and nutrient supply. It can inhibit excessive hydrolysis and fat accumulation by regulating HSL and ATGL expression and by mediating LDs formation.