Contextual and individual factors associated with traumatic dental injuries in deprived 12-year-old schoolchildren: A cohort study.

AIM: Traumatic dental injuries (TDIs) among children and adolescents have been acknowledged as of public health concern worldwide. The aim of the study was to assess the relationship between contextual and individual characteristics and TDIs in 12-year-old schoolchildren. MATERIALS AND METHODS: A cohort study was conducted with 355 schoolchildren living in deprived communities in the city of Manaus, Brazil. Contextual factors (place of residence and socio-economic indicators) and individual characteristics, including sex, family income, parents/guardians years of schooling, overjet and open bite (Dental Aesthetic Index), self-esteem (Rosenberg Self-Esteem Scale), sense of coherence (Sense of Coherence Scale), oral health beliefs, social support (Social Support Appraisals) were assessed at baseline. TDIs were measured at baseline and at 2-year follow-up using the O'Brien Index. Data were analysed through confirmatory factor analysis and structural equation modeling. RESULTS: The baseline prevalence of TDIs was 17.6% and the incidence of TDIs at 2-year follow-up was 26.8%. Better psychosocial status had a direct protective effect on the incidence of TDIs (ß = -.184). Better contextual characteristics (ß = -.135) and greater overjet (ß = -.203) were directly associated with poor psychosocial status. Higher schooling of parents/guardians directly predicted better psychosocial status (ß = .154). Psychosocial status mediated the relationship of greater overjet (ß = .036), contextual factors (ß = .024) and parental/guardian schooling (ß = -.027) with TDIs. CONCLUSIONS: Contextual factors and individual characteristics predicted TDIs. Psychosocial status was a relevant individual attribute in the causal network of TDIs, due to the direct effect on the incidence of TDIs as well as a mediator on the influence of contextual factors, overjet and parents/guardians schooling on the incidence of TDIs.

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons.

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

Comfort food concepts and contexts in which they are used: A scoping review protocol.

OBJECTIVE: The objectives of this study are to clarify the scientific definition of comfort food, identify which methodologies are being used in research on this topic and which factors are associated with the consumption of comfort food. INTRODUCTION: The consumption of comfort foods is subjective and influenced by individual experiences, as they are known and appreciated by the person. However, divergences about the definition of comfort food in the scientific literature reflect the heterogeneity of the methods used in the research, and consequently identification of possible factors associated with the consumption of this type of food, which can influence the knowledge about the consumption of these foods and their potential effects on the health of those who consume them. INCLUSION CRITERIA: Works with a qualitative and quantitative approach published in full in indexed sources or in gray literature, available online in the databases consulted, without restriction on language or year of publication will be included. METHODS: The protocol was built based on the methodological recommendations of the Joanna Briggs Institute (JBI) for scoping reviews and the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The Participants, Concept and Context (PCC) mnemonic strategy was built: general population, comfort food concept and world context. Based on this, search strategies were developed for different databases. Instruments were also developed for recording documents, extracting data, justifying the exclusion of documents and not obtaining access to content. A Pilot Study was conducted to test the developed methodology and instruments. The protocol has been registered with the Open Science Framework (OSF) (https://osf.io/gnza4/). The results will be presented in the review resulting from this protocol in three ways: accounting of the documents will be recorded in a PRISMA Flow Diagram, the main information of the studies and their frequencies will be presented in a table, and the union of these outcomes will be presented visually in a Graphical Abstract.

Assessment of sow herd frequency of PCV-2 using placental umbilical cord serum and serology in 18 breeding farms in Brazil.

Porcine circovirus type 2 (PCV-2) is the agent of one of the most important diseases in the swine industry. Although it has been controlled through vaccination, viremic piglets at birth may represent a risk by reducing vaccination efficacy. Since there are few reports on the viremic status of pre-suckling piglets regarding PCV-2 infection, we assessed the PCV-2 frequency in sows housed in 18 breeding farms with no history of clinical PCVAD in Brazil, using placental umbilical cord serum (PUCS). The selection criteria were: breeding farms with more than 1,000 sows; sows not vaccinated for PCV-2 at least for 2 years prior to the study; farms with no history of PCV-2 clinical disease in the last 12 months; and production systems with a maximum of two sites. Blood from the umbilical cords in sow placenta or directly from piglet's immediately after birth was collected from 30 litters on each farm for PCR. In addition, blood from 538 sows was collected for PCV-2 antibody detection. A total of 17.29% of the PUCS tested positive. The PCV-2 DNA was detected in PUCS from 94.4% of all farms. A total of 94.8% of the sows was positive for PCV-2 antibodies. However, seronegative sows were detected in 44.4% of farms. All 18 farms had at least 46.9% seropositive dams. A higher percentage of seronegative sows was observed for farms with more than 10% of PCV-2-positive litters compared to those with ≤10% of PCV-2 positive litters (8.9 +/-1.7% vs. 1.5 +/- 0.7%, p < 0.01, respectively).

Immune reconstitution inflammatory syndrome-associated lymphoma: A retrospective Brazilian cohort.

After initiating combined antiretroviral therapy (cART), individuals with human immunodeficiency virus (HIV) may develop Hodgkin/non-Hodgkin lymphoma due to immune reconstitution inflammatory syndrome (IRIS). This retrospective cohort study evaluated the incidence, clinical features and prognosis of IRIS-associated lymphomas in Brazilian patients. Incidence in 2000-2019 was 9.8% (27/276 patients with HIV and lymphoma; viral load drop >1 log). Time between HIV diagnosis and cART initiation was <1 year in 70.3% of cases. Time between cART initiation and lymphoma diagnosis was <3 months in 11 cases and 3-6 months in 16 cases. Overall and progression-free survival rates were similar between cases of non-IRIS-associated lymphoma and IRIS-associated lymphoma.

The association between malocclusion and health-related quality of life in adolescents: A mediation analysis.

This study investigated the role of oral health-related functional limitations and social well-being, self-perceived health, psychosocial factors, and social support in mediating the impact of malocclusion on health-related quality of life (HRQoL). A school-based 6-month cohort study was conducted with 376 12-year-old deprived adolescents. Measures at baseline included malocclusion (DAI score), dental caries, sociodemographic characteristics, psychosocial traits (self-esteem, sense of coherence, oral health beliefs), and social support. The oral health-related functional limitations and symptoms (social well-being) domains of the CPQ11-14 , self-perceived health, and HRQoL (Kiddo-KINDL) were evaluated at the 6-month follow-up. Associations between observed and latent variables (social support, psychosocial factors, and HRQoL) were evaluated using structural equation modelling, according to the Wilson and Cleary theoretical model. Malocclusion was indirectly associated with worse HRQoL, mediated by functional limitations, social well-being, and self-perceived health. Better psychosocial status was directly associated with better HRQoL, and higher social support was indirectly associated with better HRQoL via psychosocial factors. Dental caries experience, female sex, and lower family income were indirectly associated with worse HRQoL. The impact of malocclusion on HRQoL was mediated by oral health-related functional limitations, social well-being, and self-perceived health. Sociodemographic and psychosocial factors, and social support also impacted HRQoL.

Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques.

A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants1,2, although they still provide protection against severe disease. Enhanced mucosal immunity may be required to block infection and onward transmission. Intranasal administration of current vaccines has proven inconsistent3-7, suggesting that alternative immunization strategies may be required. Here we show that intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 challenge. A total of 40 previously immunized rhesus macaques were boosted with a bivalent Ad26 vaccine by the intramuscular, intranasal and intratracheal routes, or with a bivalent mRNA vaccine by the intranasal route. Ad26 boosting by the intratracheal route led to a substantial expansion of mucosal neutralizing antibodies, IgG and IgA binding antibodies, and CD8+ and CD4+ T cell responses, which exceeded those induced by Ad26 boosting by the intramuscular and intranasal routes. Intratracheal Ad26 boosting also led to robust upregulation of cytokine, natural killer, and T and B cell pathways in the lungs. After challenge with a high dose of SARS-CoV-2 BQ.1.1, intratracheal Ad26 boosting provided near-complete protection, whereas the other boosting strategies proved less effective. Protective efficacy correlated best with mucosal humoral and cellular immune responses. These data demonstrate that these immunization strategies induce robust mucosal immunity, suggesting the feasibility of developing vaccines that block respiratory viral infections.

Prehospital blood transfusion in Brazil: results of the first year of implementation in an emergency medical service.

INTRODUCTION: Hemorrhagic shock is the main cause of death in the prehospital environment, which highlights the need to standardize measures aiming at bleeding control and volume replacement in this environment. In Brazil, the first prehospital packed red blood cell transfusion service started in September 2020, in Bragança Paulista, state of São Paulo. OBJECTIVES: Describe the trends and characteristics of patients who received prehospital transfusions prior to hospital treatment during the first year of operation. METHODS: A retrospective data review was made of all patients who received transfusions from the mobile intensive care unit in Bragança Paulista over one year. RESULTS: In this period, 19 patients were transfused. Since activation, the average response time was 20 min. The mean shock indexes before and after blood transfusion were 2.16 and 1.1, respectively. During the course of the 1st year of prehospital transfusions, no blood was wasted and there were no adverse effects. CONCLUSION: Introduction of the prehospital packed red blood cell transfusion service was successful, with significant improvement in hemodynamic parameters.

Up-Front ASCT Overcomes the Survival Benefit Provided by HDAC-Based Induction Regimens in Mantle Cell Lymphoma: Data from a Real-Life and Long-Term Cohort.

BACKGROUND: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients. METHODS: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients. RESULTS: The median age at diagnosis was 65 years (38-89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%, p = 0.289). Up-front ASCT was independently associated with increased OS (p < 0.001), EFS (p = 0.005), and lower POD-24 rates (p < 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS. CONCLUSIONS: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort.

Prevalence of dental caries, periodontal disease, malocclusion, and tooth wear in indigenous populations in Brazil: a systematic review and meta-analysis.

The aim of this review was to evaluate the prevalence of dental caries, periodontal disease, malocclusion, and tooth wear in indigenous in Brazil. A systematic review of observational studies was performed according to the PRISMA guidelines (CRD42020218704). The search strategy involved the electronic databases of Embase, LILACS, PubMed, Web of Science, Scopus, and the CAPES Theses and Dissertations for gray literature. The eligibility criteria consisted of publications that assessed the prevalence of oral conditions in indigenous populations in Brazil. Studies with indigenous people living in urban area were excluded. The risk of bias was evaluated by using JBI Critical Appraisal for prevalence studies. Thirty studies were included in the review, and the majority showed a low risk of bias. A meta-analysis of 20 studies was conducted using the random-effects model and a 95% confidence interval. Several ethnicities were studied in isolation or in groups (n = 7,627 for dental caries; n = 2,774 for periodontal disease; n = 1,067 for malocclusion; n = 150 for tooth wear). The prevalence of caries ranged from 50% among indigenous people aged 18-36 months to 100% among those aged 65-74 years. The prevalence of periodontal disease ranged from 58% to 83%. The prevalence of malocclusion was 43%. Tooth wear was assessed in only one ethnic group and showed a prevalence of 100% in indigenous people aged >18 years. The certainty of evidence assessed by the GRADE system ranged from very low to moderate. This systematic review showed significant differences in the prevalence of dental caries, periodontal disease and malocclusion between indigenous population groups and territories in which indigenous people live.

Sirtuins: The NAD+-Dependent Multifaceted Modulators of Inflammation.

Significance: Sirtuins are NAD+-dependent histone deacetylases regulating important processes in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis. Recent Advances: Despite initially being discovered to regulate transcription and life span via histone deacetylase activities, emerging data continually uncover new targets and propose additional roles. Due to the outstanding importance of the sirtuins in the control of the inflammatory response, their roles in the pathogenesis of several inflammatory-based diseases have become an area of intense research. Although sirtuins have been traditionally regarded as anti-inflammatory players, several recent findings suggest that their role in inflammation is complex and that in some cases sirtuins can indeed promote inflammation. Critical Issues: In this article, we provide an update on the latest findings concerning the new mechanisms of action and concepts about the role of sirtuins during inflammation. We focus on the impact that inflammatory-based processes exert on the liver, adipose tissue, and nervous system as well as on macrophage function and activation. Also, we discuss available data pointing to the dual role that, in particular contexts, sirtuins may have on inflammation control. Future Directions: Since the knowledge of sirtuin impact on metabolism is continually expanding, new venues of research arise. Besides become being regarded as candidates of therapeutic targets, posttranscriptional control of sirtuin expression by means of microRNAs challenges our traditional concepts of sirtuin regulation; importantly, the emerging role of NAD+ metabolism in aging and longevity has added a new dimension to the interest in sirtuin function. Antioxid. Redox Signal. 39, 1185-1208.

The NADase CD38 may not dictate NAD levels in brain mitochondria of aged mice but regulates hydrogen peroxide generation.

Aging is a time-related functional decline that affects many species. One of the hallmarks of aging is mitochondrial dysfunction, which leads to metabolic decline. The NAD decline during aging, in several tissues, correlates with increase in NADase activity of CD38. Knock out or pharmacological inhibition of CD38 activity can rescue mitochondrial function in several tissues, however, the role of CD38 in controlling NAD levels and metabolic function in the aging brain is unknown. In this work, we investigated CD38 NADase activity controlling NAD levels and mitochondrial function in mice brain with aging. We demonstrate that NADase activity of CD38 does not dictate NAD total levels in brain of aging mice and does not control mitochondrial oxygen consumption nor other oxygen parameters markers of mitochondrial dysfunction. However, for the first time we show that CD38 regulates hydrogen peroxide (H2O2) generation, one of the reactive oxygen species (ROS) in aging brain, through regulation of pyruvate dehydrogenase and alfa-ketoglutarate dehydrogenase, as mitochondria H2O2 leakage sites. The effect may be related to mitochondrial calcium handling differences in CD38 absence. Our study highlights a novel role of CD38 in brain energy metabolism and aging.

Extranodal NK-/T-cell lymphoma, nasal type: what advances have been made in the last decade?

Extranodal NK-/T-cell lymphoma (ENKTCL) is a rare and highly aggressive malignancy with significant racial and geographic variations worldwide. In addition to the formerly "nasal-type" initial description, these lymphomas are predominantly extranodal in origin and typically cause vascular damage and tissue destruction, and although not fully understood, Epstein-Barr virus (EBV) has an important role in its pathogenesis. Initial assessment must include a hematopathology review of representative and viable tumor areas without necrosis for adequate immunohistochemistry studies, including EBV-encoded small RNA (EBER) in situ hybridization (ISH). Positron emission tomography with 18-fluorodeoxyglucose (18F-FDG-PET/CT) for accurate staging is essential, and most patients will have localized disease (IE/IIE) at diagnosis. Apart from other T-cell malignancies, the best treatment even for localized cases is combined modality therapy (chemotherapy plus radiotherapy) with non-anthracycline-based regimens. For advanced-stage disease, l-asparaginase-containing regimens have shown improved survival, but relapsed and refractory cases have very poor outcomes. Nowadays, even with a better understanding of pathogenic pathways, up-front therapy is completely based on chemotherapy and radiotherapy, and treatment-related mortality is not low. Future strategies targeting signaling pathways and immunotherapy are evolving, but we need to better identify those patients with dismal outcomes in a pre-emptive way. Given the rarity of the disease, international collaborations are urgently needed, and clinical trials are the way to change the future.

Targeted therapy with nanatinostat and valganciclovir in recurrent EBV-positive lymphoid malignancies: a phase 1b/2 study.

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine the recommended phase 2 dose (RP2D) for phase 2 expansion. Phase 2 patients (n = 30) received RP2D (nanatinostat 20 mg daily, 4 days per week with valganciclovir 900 mg orally daily) for 28-day cycles. The primary end points were safety, RP2D determination (phase 1b), and overall response rate (ORR; phase 2). Overall, 55 patients were enrolled (B-non-Hodgkin lymphoma [B-NHL], [n = 10]; angioimmunoblastic T-cell lymphoma-NHL, [n = 21]; classical Hodgkin lymphoma, [n = 11]; and immunodeficiency-associated lymphoproliferative disorders, [n = 13]). The ORR was 40% in 43 evaluable patients (complete response rate [CRR], 19% [n = 8]) with a median duration of response of 10.4 months. For angioimmunoblastic T-cell lymphoma-NHL (n = 15; all refractory to the last prior therapy), the ORR/CRR ratio was 60%/27%. The most common adverse events were nausea (38% any grade) and cytopenia (grade 3/4 neutropenia [29%], thrombocytopenia [20%], and anemia [20%]). This novel oral regimen provided encouraging efficacy across several EBV+ lymphoma subtypes and warrants further evaluation; a confirmatory phase 2 study (NCT05011058) is underway. This phase 1b/2 study is registered at www.clinicaltrials.gov as #NCT03397706.

Identification of miRnas with possible prognostic roles for HAM/TSP.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1-infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.

Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy: A Case Study.

Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.

A nitroalkene derivative of salicylate alleviates diet-induced obesity by activating creatine metabolism and non-shivering thermogenesis.

Obesity-related type II diabetes (diabesity) has increased global morbidity and mortality dramatically. Previously, the ancient drug salicylate demonstrated promise for the treatment of type II diabetes, but its clinical use was precluded due to high dose requirements. In this study, we present a nitroalkene derivative of salicylate, 5-(2-nitroethenyl)salicylic acid (SANA), a molecule with unprecedented beneficial effects in diet-induced obesity (DIO). SANA reduces DIO, liver steatosis and insulin resistance at doses up to 40 times lower than salicylate. Mechanistically, SANA stimulated mitochondrial respiration and increased creatine-dependent energy expenditure in adipose tissue. Indeed, depletion of creatine resulted in the loss of SANA action. Moreover, we found that SANA binds to creatine kinases CKMT1/2, and downregulation CKMT1 interferes with the effect of SANA in vivo. Together, these data demonstrate that SANA is a first-in-class activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue and emerges as a candidate for the treatment of diabesity.