Prognostic Relevance of Recurrent Sites of Gastric Cancer Treated With Curative Resection: A Single Center Retrospective Study.

PURPOSE: Gastric cancer treated with curative resection exhibits several recurrence patterns. The peritoneum is the most common site of recurrence. Some reports have indicated different prognostic influences according to the recurrence sites in other cancers, such as esophageal and colorectal cancers. This study investigated whether the recurrence sites influenced the prognosis of patients with recurrent gastric cancer. MATERIALS AND METHODS: The data of 115 patients who experienced tumor recurrence after curative gastrectomy were retrospectively reviewed. The sites of recurrence were divided into 4 groups: lymph node (LN), peritoneum, other single organs, and multiple lesions. Clinicopathological features were compared between the sites of recurrence. Prognosis after resection and recurrence were also compared. RESULTS: The peritoneum was the primary site of recurrence in 38 patients (33%). The tumor differentiation and pathological stages were significantly different. Survival after surgery did not show a statistically significant difference (hazard ratio [HR] of LN: 1, peritoneum: 1.083, other single organs: 1.025, and multiple lesions: 1.058; P=1.00). Survival after recurrence was significantly different (HR of LN, 1; peritoneum, 2.164; other single organs, 1.092; multiple lesions, 1.554; P=0.01), and patients with peritoneal and multiple lesion recurrences had worse prognosis. Furthermore, peritoneal recurrence seemed to occur later than that at other sites; the median times to recurrence in LN, peritoneal, other single-organ, and multiple lesions were 265, 722, 372, and 325 days, respectively. CONCLUSIONS: The sites of gastric cancer recurrence may have different prognostic effects. Peritoneal recurrence may be less sensitive to chemotherapy and occur during the late phase of recurrence.

Prognostic Impact of Post-operative Infectious Complications in Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: Post Hoc Analysis of a Randomized Controlled Trial, JCOG0501.

PURPOSE: Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer. METHODS: The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses. RESULTS: There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655-2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226-1.456)). CONCLUSION: This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected.

A Retrospective Study of Gemcitabine Plus Nab-Paclitaxel for Advanced Pancreatic Cancer Refractory to Gemcitabine Monotherapy.

BACKGROUND/AIM: This study aimed to investigate the efficacy and safety of gemcitabine (GEM) plus nab-paclitaxel (nab-PTX), termed GnP, which is limited, in patients with advanced pancreatic cancer (PC) who show good tolerance to GEM monotherapy prior to being refractory to it. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with locally advanced or metastatic PC who received GEM followed by GnP between December 2014 and March 2019, regardless of the treatment line. RESULTS: A total of 14 patients who received GnP after becoming refractory to GEM were included in this study. Eight patients were included in the nab-PTX-naïve group, seven of whom were treated with GEM monotherapy as first-line chemotherapy, and one was refractory to GEM monotherapy after modified FOLFIRINOX treatment. The other six patients were included in the nab-PTX reintroduction group. In this group, all patients received GnP followed by GEM maintenance therapy to prevent adverse events, such as peripheral neuropathy and fatigue. Two patients in the nab-PTX-naïve group showed partial response and none in the reintroduction group; median progression-free survival was 7.6 and 1.4 months and median overall survival was 9.4 and 6.2 months, respectively. In the safety analysis, grade 3 anemia and peripheral neuropathy were observed in one patient in the nab-PTX reintroduction group, while the remaining adverse events were of grade 1 or 2. CONCLUSION: GnP is safe and effective even in patients with GEM-refractory PC, and GEM treatment followed by GnP can be an effective treatment option for patients with nab-PTX-naïve PC.

Prognostic effect of categorized tumor deposits in gastric cancer: A single-center retrospective study.

BACKGROUND: Tumor deposits are defined as all types of isolated cancer lesions without lymphocyte aggregates considered part of the lymph node. Tumor deposits have been reported as a negative prognostic factor. However, the survival significance of categorized tumor deposits is uncertain, particularly in gastric cancer. This study aimed to investigate the prognostic difference among categorized tumor deposits. METHODS: Patients who underwent gastrectomy for gastric cancer were enrolled. All tumor deposits were categorized into irregular nodule, irregular nodule star, smooth nodule, and vascular/neural invasion. There are some cases with more than 2 categorized tumor deposits. These cases were categorized as tumor deposit complex in the following analysis. We performed survival analysis between the patients with and without tumor deposits, and compared the survival among each categorized tumor deposit. RESULTS: Of 868 patients, there were 96 (11.1%) and 772 (88.9%) patients with and without tumor deposits. Vascular/neural invasion, smooth nodule, irregular nodule, irregular nodule star, and the tumor deposits complex was observed in 6 (6.3%), 15 (15.6%), 43 (44.8%), 1 (1.0%), and 31 (32.3%) patients. Patients with tumor deposits displayed poorer survival than those without; the 3-year overall survival: tumor deposits negative = 87.0%, tumor deposits positive = 53.2% (P < .001). Survival analysis revealed tumor deposits can be a prognostic risk factor (hazard ratio: 1.9854, 95% confidence interval: 1.393-2.830, P < .01). Irregular nodule and the tumor deposits complex demonstrated the worst prognosis (irregular nodule 3-year overall survival: 51.2%, tumor deposits complex 3-year overall survival: 41.9%, P = .001), whereas smooth nodule demonstrated better prognosis (smooth nodule 3-year overall survival: 80%). CONCLUSION: Tumor deposits exerted a negative survival effect in gastric cancer. Irregular nodule and the tumor deposits complex displayed a strong prognostic effect.

Carbon dioxide emissions through land use change, fire, and oxidative peat decomposition in Borneo.

Borneo has accumulated an abundance of woody carbon in its forests and peat. However, agricultural land conversion accompanied by plantation development, dead wood burning, and peat drying from drainage are major challenges to climate change mitigation. This study aimed to develop a method of estimating carbon dioxide (CO2) emissions from land use change, forest and peat fires, and oxidative peat decomposition, and CO2 uptake from biomass growth across Borneo using remote sensing data from 2001 to 2016. Although CO2 uptake by biomass growth in vast forests has shown a significant increasing trend, an annual net release of 461.10 ± 436.51 (average ± 1 standard deviation) Tg CO2 year-1 was observed. The estimated emissions were predominantly characterized by land use changes from 2001 to 2003, with the highest emissions in 2001. Land use change was evaluated from annual land use maps with an accuracy of 92.0 ± 1.0% (average ± 1 standard deviation). Forest and peat fires contributed higher emissions in 2002, 2006, 2009, 2014, and 2015 compared to other years and were strongly correlated with the Southern Oscillation Indexes. These results suggest that more CO2 may have been released into the atmosphere than previously thought.

Clinical Complete Response of Recurrent Gastric Cancer after Third-line CPT-11 Chemotherapy.

A 75-year-old man underwent distal gastrectomy for advanced gastric cancer in September 2018. During the adjuvant chemotherapy, computed tomography (CT) revealed recurrence sites in the liver and para-aortic lymph nodes. Therefore, chemotherapy was initiated. After first-line (capecitabine with oxaliplatin) and second-line (paclitaxel with ramucirumab) treatments, nivolumab was used as third-line chemotherapy. This treatment showed a strong effect against the tumor. However, following an immune-related adverse effect (irAE) because of nivolumab, the therapy was halted. The irAE was diagnosed with central adrenal insufficiency that was controllable by oral intake of steroids. CPT-11 was started and showed a similarly strong effect to that observed for nivolumab. Eventually, the recurrent tumor lesions became too small to be detected by CT. We discontinued CPT-11 at the request of the patient. Even after discontinuation, no recurrent sites have been observed, allowing us to declare a case of clinical complete response (cCR). In conclusion, even if irAEs occur in a patient, continuing chemotherapy should be considered. However, if cCR is achieved, discontinuation of chemotherapy might be a strategic treatment option.

Discovery of TP0597850: A Selective, Chemically Stable, and Slow Tight-Binding Matrix Metalloproteinase-2 Inhibitor with a Phenylbenzamide-Pentapeptide Hybrid Scaffold.

Matrix metalloproteinase-2 (MMP2) is a zinc-dependent endopeptidase and a promising target for various diseases, including cancer and fibrosis. Herein, we report the discovery of a novel MMP2-selective inhibitor with high chemical stability and slow tight-binding features. Based on the degradation mechanism of our small-molecule-peptide hybrid 1, the tripeptide linker {5-aminopentanoic acid [Ape(5)]-Glu-Asp} of 1 was replaced by a shorter linker (γ-D-Glu). Phenylbenzamide was suitable for the new generation of MMP2 inhibitors as an S1' pocket-binding group. The introduction of (4S)-aminoproline dramatically increased the chemical stability while maintaining high subtype selectivity because of its interaction with Glu130. TP0597850 (18) exhibited high stability over a wide range of pH values as well as potent MMP2 inhibition (Ki = 0.034 nM) and ≥2000-fold selectivity determined using the inhibition constants. A kinetic analysis revealed that it possesses slow tight-binding nature with a long MMP2 dissociative half-life (t1/2 = 265 min).

Evaluating the optimal treatment strategy for early and advanced remnant gastric cancer.

BACKGROUND: This study assessed lymph node metastasis characteristics to investigate the optimal treatment strategy for early and advanced remnant gastric cancer (RGC). METHODS: Cases of completion gastrectomy for RGC were enrolled. The frequency of lymph node metastasis was investigated, and risk factors for metastasis were identified. The clinical significance of completion gastrectomy in early remnant gastric carcinoma cases was also examined. In advanced cases, 3-year survival was analysed to investigate the prognostic importance of lymph node dissection and splenectomy. RESULTS: Seventy-nine patients were included. Lymphatic invasion and pathological tumour depth were identified as risk factors for lymph node metastasis. There was no metastasis in the pT1 cases. In advanced cases, the incidence of lymph node #10 and jejunal lymph node metastasis was 8.3-10.0% and 17.6%, respectively. Prognosis was found to be unrelated with splenectomy. CONCLUSIONS: Lymphatic invasion and pathological T status were identified as risk factors for LN metastasis in RGC. Additional gastrectomy after ESD might not be mandatory for early RGC cases. For advanced RGC cases, splenectomy might not improve patient prognosis, however, lymph node dissection of jejunal and #10 lymph nodes should be considered due to its high incidence of metastasis.

XAF1 overexpression exacerbates diabetes by promoting pancreatic ß-cell apoptosis.

AIMS: Pancreatic ß-cell apoptosis may be involved in the onset and progression of type 2 diabetes mellitus, although its mechanism remains unclear. We previously demonstrated that macrophage-derived interferon (IFN) ß induced X-linked inhibitor of apoptosis-associated factor 1 (XAF1) expression in ß-cells and accelerated ß-cell apoptosis in vitro. Here, we explored the effects of XAF1 on ß-cell function and progression of diabetes in vivo. METHODS: Pancreatic ß-cell-selective XAF1 overexpressing (Xaf1 Tg) mice were generated. Xaf1 Tg mice and their wild-type (WT) littermates were fed either a normal diet or a 40% or 60% high-fat diet (HFD). The effects of ß-cell XAF1 on ß-cell apoptosis and exacerbation of diabetes were investigated. RESULTS: Palmitic acid induced IFNß expression in macrophages, and HFD intake promoted macrophage infiltration in pancreatic islets, both of which cooperatively upregulated XAF1 expression in mouse islets. Furthermore, HFD-fed Xaf1 Tg mice demonstrated increased ß-cell apoptosis, lowered insulin expression, and impaired glucose tolerance compared with WT mice fed the same diet. These effects were more pronounced in the 60%HFD group than in the 40%HFD group. CONCLUSIONS: Pancreatic ß-cell XAF1 expression was enhanced via HFD-induced, macrophage-derived IFNß, which promoted ß-cell apoptosis and led to a reduction in insulin secretion and progression of diabetes. To our knowledge, this is the first report to demonstrate an association between pancreatic ß-cell XAF1 overexpression and exacerbation of diabetes, thus providing insight into the mechanism of ß-cell mass reduction in diabetes.

Discovery of Aryloxyphenyl-Heptapeptide Hybrids as Potent and Selective Matrix Metalloproteinase-2 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis.

Matrix metalloproteinase-2 (MMP2) is a zinc-dependent endopeptidase that plays important roles in the degradation of extracellular matrix proteins. MMP2 is considered to be an attractive target for the treatment of various diseases such as cancer, arthritis, and fibrosis. In this study, we have developed a novel class of MMP2-selective inhibitors by hybridizing the peptide that binds to a zinc ion and S2-S5 pockets with small molecules that bind to the S1' pocket. Structural modifications based on X-ray crystallography revealed that the introduction of 2,4-diaminobutanoic acid (Dab) at position 4 dramatically enhanced MMP2 selectivity by forming an electrostatic interaction with Glu130. After improving the metabolic and chemical stability, TP0556351 (9) was identified. It exhibited potent MMP2 inhibitory activity (IC50 = 0.20 nM) and extremely high selectivity. It suppressed the accumulation of collagen in a bleomycin-induced idiopathic pulmonary fibrosis model in mice, demonstrating the efficacy of MMP2-selective inhibitors for fibrosis.

Assessing the Prognostic Value of Extranodal Extension in Esophageal Cancer from the Pathological Staging Perspective.

BACKGROUND: Extranodal extension (ENE) is a prognostic factor for several types of malignant tumors, including esophageal cancer. Although the prognostic value of ENE has been investigated in esophageal cancer, its clinical utility warrants further investigation. MATERIALS AND METHODS: This retrospective single-center study evaluated 105 patients who underwent esophagectomy and had histologically node-positive metastasis between January 2007 and June 2017. The abilities of ENE to predict overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank test, as well as Cox proportional hazard models. Subgroup analyses of ENE's prognostic value were performed according to each pathological tumor-node-metastasis category. RESULTS: Significant differences according to ENE status were observed in the Kaplan-Meier analyses of OS (p = 0.001) and DFS (p = 0.001), as well as in the Cox proportional hazards models for OS (p = 0.009) and DFS (p = 0.012). Relative to patients without ENE, patients with ENE had significantly poorer OS if they also had pT3 status, pN1 status, or pathological stage III disease. However, no significant differences were observed in the subgroup analyses of pN3 status and pathological stage IV disease. CONCLUSIONS: Among patients with esophageal cancer, ENE status can predict a poor prognosis and may be useful for patient stratification. However, the prognostic value of ENE status may be limited to patients with specific pathological factors.

The Link Between Periodontal Inflammation and Obesity.

PURPOSE OF REVIEW: Obesity is a trigger for multiple diseases such as diabetes mellitus, hypertension, and cardiovascular diseases. Epidemiological studies have shown that obesity may be a risk factor for periodontal disease. Recently, there have been reports of presumed mechanisms of the associations between periodontitis and lipid metabolism or thermogenesis. This review aims to discuss the link between periodontal disease and energy regulatory function based on recent findings. RECENT FINDINGS: It has been demonstrated that activation of the C-C motif chemokine ligand/C-C chemokine receptor 7 pathway in adipose tissue induces inflammation and impairment of lipid metabolism and energy regulation in mice. Porphyromonas gingivalis administration has been shown to induce further weight gain and increased adipose tissue in diet-induced obese mice. Additionally, it has been reported that Porphyromonas gingivalis-induced endotoxemia potentially affect obesity by altering endocrine functions in brown adipose tissue in mice. Several cohort studies have shown that obesity is associated with tooth loss 5 years later, and periodontal conditions of obese individuals are significantly worse 2 and 6 months after the treatment compared with those of non-obese individuals. It has also been reported that body mass index is positively associated with the periodontal inflamed surface area index, a measure of periodontal inflammation. These results suggest that not only the enhancement of inflammation due to obesity but also the activation of inflammatory signaling may affect energy regulation. SUMMARY: Loss of adipose tissue homeostasis induces increase and activation of immune cells in adipose tissue, leading to impaired immune function in obesity. Various cytokines and chemokines are secreted from obese adipose tissue and promote inflammatory signaling. Some of these signaling pathways have been suggested to affect energy regulation. The combination of obesity and periodontitis amplifies inflammation to levels that affect the whole body through the adipose tissue. Obesity, in turn, accelerates the exacerbation of periodontitis.

Adipose-specific C-C motif chemokine ligand (CCL) 19 overexpression drives the mice to both insulin resistance and weight gain.

INTRODUCTION: Enlarged adipose tissue is characterized by infiltration of activated immune cells and increased expression of chemokines recruiting these cells including C-C motif ligand 19 (CCL19), although the role of adipose CCL19 is still inconclusive. RESEARCH DESIGN AND METHODS: Adipocyte-specific Ccl19 knock-in (KI) mice were generated, and the mice were fed either a normal diet or 40% or 60% fat diet (FD) to investigate the effects of CCL19 on the induction of inflammation and lipid metabolism. RESULTS: Ccl19KI mice exhibited increased inflammatory signs in adipose tissue and enlarged subcutaneous white and brown adipose tissue than those of wild-type (WT) mice. The adipose tissue of Ccl19KI mice was characterized by increased extracellular signal-regulated kinase 1/2 and decreased AMP-activated protein kinase α phosphorylation. The protein expression of peroxisome proliferator-activated receptor γ coactivator 1α and uncoupling protein 1 was significantly reduced in brown adipose tissue of Ccl19KI mice compared with that in WT mice. The most remarkable changes between genotypes were observed in mice fed a 40% FD. CONCLUSION: A 40% FD enhanced the effects of CCL19 overexpression, and these mice could be a suitable model to study metabolic disorders in overweight Asians.

First comprehensive quantification of annual land use/cover from 1990 to 2020 across mainland Vietnam.

Extensive studies have highlighted a need for frequently consistent land cover information for interdisciplinary studies. This paper proposes a comprehensive framework for the automatic production of the first Vietnam-wide annual land use/land cover (LULC) data sets (VLUCDs) from 1990 to 2020, using available remotely sensed and inventory data. Classification accuracies ranged from 85.7 ± 1.3 to 92.0 ± 1.2% with the primary dominant LULC and 77.6 ± 1.2% to 84.7 ± 1.1% with the secondary dominant LULC. This confirmed the potential of the proposed framework for systematically long-term monitoring LULC in Vietnam. Results reveal that despite slight recoveries in 2000 and 2010, the net loss of forests (19,940 km2) mainly transformed to croplands over 30 years. Meanwhile, productive croplands were converted to urban areas, which increased approximately ten times. A threefold increase in aquaculture was a major driver of the wetland loss (1914 km2). The spatial-temporal changes varied, but the most dynamic regions were the western north, the southern centre, and the south. These findings can provide evidence-based information on formulating and implementing coherent land management policies. The explicitly spatio-temporal VLUCDs can be benchmarks for global LULC validation, and utilized for a variety of applications in the research of environmental changes towards the Sustainable Development Goals.

Laparoscopic mediastinal approach for retrosternal gastric conduit cancer after esophagectomy.

The prognosis of esophageal cancer has improved, but the incidence of gastric conduit cancer has increased. Gastric conduit cancer is difficult to treat because current treatment options are highly invasive; in particular, surgical procedures have high mortality and modality. Treatment through the retrosternal route usually requires sternotomy, which often causes lethal osteomyelitis. To prevent lethal complications and reduce invasiveness, we used the laparoscopic mediastinal approach. Here, we report a successful case using the laparoscopic mediastinal approach for the treatment of gastric conduit cancer through the retrosternal route. Despite a few concerns, this approach can be a treatment option for gastric conduit cancer through the retrosternal route.

Prognostic value of tumor regression grade following the administration of neoadjuvant chemotherapy as treatment for gastric/gastroesophageal adenocarcinoma: A meta-analysis of 14 published studies.

INTRODUCTION: The efficacy of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (GC) has recently been revealed. The use of tumor regression grade (TRG) has also been reported, where TRG has been positively correlated with prognosis. However, previous studies included several types of GC and treatments. The prognostic value of TRG in a specific population has not been well investigated. Therefore, a meta-analysis of studies on gastric adenocarcinomas treated with NAC that evaluate the prognostic impact of TRG on overall survival (OS) must be conducted to provide more accurate evidence. METHODS: A meta-analysis of studies reporting gastric cancer/gastroesophageal junction (GC/GEJ) adenocarcinoma treated with NAC was performed. Studies that calculate the number of responders and non-responders were considered eligible. The risk ratio (RR) was obtained from the eligible studies, and a random-effects model was used for pooled analysis. RESULTS: Fourteen studies, which included a total of 1660 patients, were included in the current study. The responders showed better OS (RR: 0.53, 95% confidence interval (CI): 0.46-0.60, P < 0.001). All subgroup analyses (Asian vs. non-Asian populations, different TRGs, GC/GEJ vs. GC) also revealed the statistical dominance of better TRG over better OS. However, the possibility of some publication bias remained. CONCLUSIONS: In this meta-analysis, better TRG was associated with better OS. However, the histology, configuration, and location of GC varied. Hence, a more subdivided analysis is recommended to obtain more solid evidence.

Intraoperative blood loss as an independent prognostic factor for curative resection after neoadjuvant chemotherapy for gastric cancer: a single-center retrospective cohort study.

PURPOSE: Surgery-induced factors such as postoperative infectious complications (PICs) and intraoperative blood loss (IBL) have a negative impact on the survival of patients undergoing surgery for gastric cancer. A recent study showed that neoadjuvant chemotherapy (NAC) could reduce the negative impact of PICs; hence, we conducted the present study to investigate if NAC can also reduce the negative prognostic impact of IBL. METHODS: We reviewed 115 gastric cancer patients treated with NAC and radical gastrectomy. The cut-off for IBL predicting the long-term survival was assessed by a receiver operating characteristic curve. The Cox proportional hazard model was used to evaluate the association between patient characteristics including IBL, overall survival, and disease-free survival. RESULTS: The cut-off for IBL was set at 990 ml. Twenty-six patients had excessive IBL exceeding 990 ml (22.6%) and PICs developed in 33 patients (28.7%). The body mass index, IBL, ypT, and ypN were significant independent prognostic predictors, but PICs were not. CONCLUSION: NAC did not decrease the risk induced by excessive IBL. The prophylactic effect of NAC on surgery-induced risk was inconsistent.

Quantum Tunneling of a He Atom Above and Below a Benzene Ring.

Van der Waals (vdW) complexes with helium atoms have deserved much attention for their intriguing quantum nature relevant to microscopic superfluidity. However, tunneling splitting, the clear signature of quantum delocalization of He atoms, has rarely been identified in any of the He-containing complexes. Here, UV excitation spectra of benzene-He were extensively examined with almost full rotational resolution to identify two weak vibronic bands with vibrational excitation energies of only ∼13 and ∼16 cm-1. Each of rotational transitions appears to be split into doublets in the higher-frequency band. This splitting is attributed to quantum tunneling due to the delocalization of He spread over two minimum locations below and above the benzene ring. The magnitude of the tunneling splitting as well as the vibrational frequencies of the two vdW modes are compared with the reported theoretical prediction to quantitatively assess the intermolecular potential energy surfaces so far derived.

SPOCK1 induces adipose tissue maturation: New insights into the function of SPOCK1 in metabolism.

SPOCK1 is a calcium-binding matricellular proteoglycan that has been extensively studied in several cancer cells. Previously, we generated a mouse line overexpressing SPOCK1 (Spock1-Tg mouse) and showed that SPOCK1 might play an important role in drug-induced gingival overgrowth, indicating that it possesses physiological functions in non-cancer diseases as well. Although SPOCK1 was reported to be secreted from human adipocytes, its role in adipocyte physiology has not been addressed yet. In this study, SPOCK1 protein expression was confirmed in pancreas, adipose tissues, spleen, and liver of normal diet (ND)-fed mice. Interestingly, SPOCK1 was up-regulated in the pancreas and adipose tissues of the high-fat diet (HFD)-fed mice. Spock1-Tg mice fed with ND showed increased maturation in epididymal and inguinal adipose tissues. In addition, Spock1 overexpression strongly decreased expression of UCP-1 in adipose tissues, suggesting that SPOCK1 might regulate thermogenic function through suppression of UCP-1 expression. Finally, exogenous SPOCK1 treatment directly accelerated the differentiation of 3T3-L1 adipocytes, accompanied by the up-regulation of adipocyte differentiation-related gene expression. In conclusion, we demonstrated for the first time that SPOCK1 induced adipocyte differentiation via the up-regulation of adipogenesis-related genes.