Table 3. Sensitivity analyses We determined the association between lifestyle habits and metabolic health, but considering as metabolically healthy those subjects with up to 2 risk factors sensitivity analysis 1; S3 Table. Discussion Healthy lifestyle habits could prevent or reverse a metabolically unhealthy phenotype, thus reducing the risk of cardiovascular events and all-cause mortality.

Conclusions We have shown that about one third of the Chilean population manifests a metabolically unhealthy phenotype, but this prevalence varies across nutritional statuses. Supporting information. S1 File. STROBE checklist for cross-sectional studies. s DOCX. S1 Table.

General characteristics and lifestyle habits in the overall sample. S2 Table. S3 Table. S4 Table. Acknowledgments To the Ministerio de Salud de Chile for providing the database.

References 1. Riley L, Guthold R, Cowan M, Savin S, Bhatti L, Armstrong T, et al. The World Health Organization STEPwise Approach to Noncommunicable Disease Risk-Factor Surveillance: Methods, Challenges, and Opportunities. Am J Public Health. Wang B, Zhuang R, Luo X, Yin L, Pang C, Feng T, et al.

Prevalence of Metabolically Healthy Obese and Metabolically Obese but Normal Weight in Adults Worldwide: A Meta-Analysis. Horm Metab Res. Hinnouho G-M, Czernichow S, Dugravot A, Batty GD, Kivimaki M, Singh-Manoux A.

Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care. Ding C, Chan Z, Magkos F. Curr Opin Clin Nutr Metab Care. Stefan N, Schick F, Häring H-U. Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans.

Cell Metab. Muñoz-Garach A, Cornejo-Pareja I, Tinahones FJ. Does Metabolically Healthy Obesity Exist? Meigs JB, Wilson PWF, Fox CS, Vasan RS, Nathan DM, Sullivan LM, et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease.

J Clin Endocrinol Metab. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International.

Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population NHANES — Arch Intern Med.

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Encuesta Nacional de Salud — Informe Final. Ministerio de Salud, Gobierno de Chile. Villanueva B, Arteaga A, Maiz A, Cortés VA. Abdominal obesity is a common finding in normal and overweight subjects of Chile and is associated with increased frequency of cardiometabolic risk factors.

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Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. The participants who moved from MHO to MUO had a substantially greater risk of kidney cancer than did those in the reference group, with a multivariate-adjusted HR of 1.

In contrast, neither the stable MHO group multivariate-adjusted HR, 1. The MHNO to MUNO group and the stable MUNO group were not at increased risk of incident kidney cancer multivariate-adjusted HR, 1. Figure 1 depicts the multivariate-adjusted HRs for incident kidney cancer.

Table 3 Risks of incident kidney cancer according to the transition from metabolically healthy to unhealthy status among participants with obesity in reference to the stable MHNO group.

Associations of the obese metabolic health phenotypes with kidney cancer were generally consistent across the subgroups according to the clinical variables, including age, sex, smoking, drinking, and exercise Figure 2.

In specific, the hazardous effect of phenotypic transition from MHO to MUO was particularly evident in men and smokers multivariate-adjusted HR, 2. Across all subgroups, obese participants who stayed at metabolically heath status i.

Figure 2 Subgroup analyses for the risk of kidney cancer according to the phenotypic transitions. The covariates are excluded from the adjustment in the corresponding subgroup analyses.

This study suggests that metabolic unhealthiness could contribute to kidney cancer risk in obese patients. We found that maintaining or recovering metabolic health reduced the incidence of kidney cancer, whereas the persistence of a metabolically unhealthy status or the shift to metabolic unhealthiness substantially increased the risk of kidney cancer.

Our findings indicate that metabolic unfitness, rather than the presence of obesity, contributes to incident kidney cancer. More recently, an increased risk of kidney cancer due to obesity has been consistently reported.

In Japan, a population-based study demonstrated a U-shaped association between BMI and the risk of renal cell cancer RCC Moreover, a population-based nested case-control study reported a positive relationship between BMI and the risk of RCC among Chinese men; this study showed an increased odds ratio of 1.

Positive linear relationships were found in the South Korean population between BMI or waist circumference and the risk of incident kidney cancer In particular, individuals with both general obesity and central obesity had a 1.

These studies support the significant implication of obesity in the risk of kidney cancer. However, these studies did not take metabolic health status into consideration. Here, we found that the incident kidney cancer risk among obese individuals depended on their metabolic health status.

Based on the baseline metabolic health status, the HR for kidney cancer in the MHO group was not significantly higher than that in the MHNO group Table 2 ; Figure 1. However, when the phenotypic transition was considered, the probability of incident kidney cancer was significantly higher in individuals who were in the MHO group at baseline but transitioned to an MUO status and in those who maintained a steady MUO phenotype Table 3 , Figure 1.

In contrast, the stable MHO group or the MUO to MHO group were not at a higher risk of developing kidney cancer even though they were still obese Table 3 ; Figure 1 , which were consistently observed in subgroup analyses Figure 2. These data imply that metabolic health, not obesity itself, is a decisive factor in kidney cancer incidence.

Previously, in the MetS and cancer project, several metabolic factors or a combination of risk factors were found to be associated with an increased risk of RCC Similarly, a nationwide study in Korea reported that MetS was closely related to the risk of kidney cancer in both sexes; specifically, patients with MetS had significantly increased HRs for incident kidney cancer, and this relationship was consistent in both men and women men: HR, 1.

Collectively, metabolic disturbances induced by disproportional body fat distribution could be the main contributor to incident kidney cancer in participants with obesity. In our study, we suggested that the metabolic health status was a largely modifiable risk factor.

Prior studies have reported that approximately one-third of individuals with obesity experienced changes in their metabolic health status 25 — 28 , potentially affecting their health outcomes.

Therefore, recent studies have adopted novel approaches to reflect the influence of phenotypic transitions on diverse outcomes. For example, Kim et al. have discovered that maintaining metabolic fitness could protect the study participants from developing type 2 diabetes, regardless of their body weight Moreover, our research team discovered that phenotypic alterations in MHO increased cardiovascular risk, CKD incidence, and mortality 25 , More recently, we demonstrated that metabolic health status was a deciding factor for the occurrence of colorectal cancer, for which obesity was known as a major risk factor Herein, we added another evidence that we should consider the dynamic nature of metabolic health status in risk assessment and management in obese patients.

Although the specific mechanism through which obesity raises the risk of kidney cancer is yet to be determined, the altered circulating levels of adipokines 30 , the chronic inflammatory status 31 , and modulation of host immunosurveillance 30 , and insulin resistance leading to increased insulin and insulin-like growth factor IGF -1 levels, which are involved in carcinogenesis may play a significant role 6 , 32 , Although our results cannot establish the mechanism, our data provide evidence that metabolic unhealthiness associated with obesity plays a pivotal role in the increased risk of kidney cancer in patients with obesity.

Therefore, further investigations on the pathophysiologic changes in different metabolic health obese phenotypes are needed. This study had some limitations. First, since the study population was primarily Korean, we cannot generalize our study results to other ethnic groups.

Second, the study did not consider the phases of kidney cancer or its pathologic type. Thirdly, an accurately measured increase in lower body fat mass is now recognized as an independent indicator of metabolic health Therefore, the identification of distinct fat distribution phenotypes using relevant measurements, such as hip circumference, could provide better insight into the relationship between adiposity and cancer risk; however, we were unable to investigate the impact of these measurements on KC risk in our analyses because the NHIS data did not include any measurement for lower body fat mass.

Future study on the significance of lower body fat mass in obesity-related cancer would give greater precision to our understanding of the clinical implications of metabolic health in obese populations.

Despite these limitations, our study has strengths in that we used a large nationwide cohort and explained the effects of dynamic metabolic health on the incidence of kidney cancer in obese adults. Our methodology revealed the implication of metabolic unhealthiness on kidney cancer risk and therefore suggested that being metabolically healthy should be prioritized to lower the kidney cancer risk in obese patients.

Our findings identified metabolic unhealthiness as a risk factor for kidney cancer risk in individuals with obesity. Furthermore, our results suggest that the dynamic metabolic health status should be considered as significantly affecting the kidney cancer risk.

do , approval number: NHIS The studies involving human participants were reviewed and approved by Hallym Sacred Heart Hospital Institutional Review Board IRB. The ethics committee waived the requirement of written informed consent for participation.

Conceptualization, YC and CJ; methodology, Y-JK; software, Y-JK; validation, YC and Y-JK; formal analysis, YC and Y-JK; investigation, YC; resources, YC; data curation, CJ; writing—original draft preparation, YC; writing—review and editing, HK, J-YP, WL, Y-JK, and CJ; visualization, Y-JK; supervision, YC.

All authors have read and agreed to the published version of the manuscript. This research was supported by the Hallym University Research Fund HURF The authors thank Editage for the English language review. We would like to thank the Korean National Health Insurance Service and all the participants of the study and health check-up.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. BMI, body mass index; BP, blood pressure; FPG, fasting plasma glucose; ICD, International Classification of Diseases; IRB, Hallym Sacred Heart Hospital Institutional Review Board; MHNO, metabolically healthy non-obese; MHO, metabolically healthy obesity; MHO, metabolically healthy obesity; MUNO, metabolically unhealthy non-obese; MUO, metabolically unhealthy obesity; NHIS-HEALS, Korean National Health Insurance Service-National Health Screening Cohort; RCC, renal cell cancer.

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Global pandemics interconnected - obesity, impaired metabolic health and covid Nat Rev Endocrinol 17 3 — Stefan N, Cusi K. A global view of the interplay between non-alcoholic fatty liver disease and diabetes.

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Nat Rev Cancer 4 8 — Han SJ, Lee SH. Nontraditional risk factors for obesity in modern society. J Obes Metab Syndr 30 2 — Liu X, Sun Q, Hou H, Zhu K, Wang Q, Liu H, et al. The association between bmi and kidney cancer risk: An updated dose-response meta-analysis in accordance with prisma guideline.

Med Baltimore 97 44 :e CrossRef Full Text Google Scholar. In Statistics Canada estimated that 3. The latest discoveries in human health increasingly reveal the urgency of understanding the composition and function of the human intestinal microbiome in order to promote health and stop the spread of metabolic diseases.

Press release French only. The Canada Excellence Research Chair in the Microbiome-Endocannabinoidome Axis in Metabolic Health is the first chair in the world dedicated to the integrated study of the intestinal microbiome and its impairments with a view to understanding its influence on the molecular mechanisms underlying obesity, as well as the development of Type 2 diabetes, cardiometabolic disease, and other associated disorders.

The chair's mission is to identify new therapeutic targets and design innovative medical and nutritional strategies to maintain health and prevent certain illnesses. For more information, visit the website. A world-renowned authority in the field of the biochemistry and pharmacology of endocannabinoids, Vincenzo Di Marzo, Ph.

He earned his Ph. in biochemistry and molecular pharmacology at Imperial College in London in and completed postdoctoral studies in lipid biochemistry and natural product chemistry at ICB-CNR.

Di Marzo has received numerous research grants, including a Human Frontier Science Program grant to study the biosynthesis, metabolism, and structure-activity relationships of anadamide. He was awarded the International Cannabinoid Research Society's Mechoulam Award for his outstanding contributions to the field, and Thomson Reuters named him one of the most cited authors in the field of pharmacology and toxicology.

The Chair will study the mechanisms by which the intestinal microbiome and metabolic syndrome interact through the endocannabinoidome.

The microbiome is the complex system comprising the intestinals microbial population as well as its dynamics, structure, and functions. The endocannabinoidome is a network of chemical signals linked to the endocannabinoid system, which plays a role in regulating and stabilizing bodily functions.

Di Marzo has received numerous research grants, including a Human Frontier Science Program grant to study the biosynthesis, metabolism, and structure-activity relationships of anadamide.

He was awarded the International Cannabinoid Research Society's Mechoulam Award for his outstanding contributions to the field, and Thomson Reuters named him one of the most cited authors in the field of pharmacology and toxicology. The Chair will study the mechanisms by which the intestinal microbiome and metabolic syndrome interact through the endocannabinoidome.

The microbiome is the complex system comprising the intestinals microbial population as well as its dynamics, structure, and functions. The endocannabinoidome is a network of chemical signals linked to the endocannabinoid system, which plays a role in regulating and stabilizing bodily functions.

Since the intestinal microbiome is closely linked to diet, it is important to study how diet influences its structure and functions in order to understand how it influences cardiometabolic health. The Chair intends to deepen and expand knowledge on the subject by examining several questions simultaneously, including the following:.

To answer these questions, Pr. Di Marzo will assemble a high-calibre research team at Université Laval to work closely with the International Joint Unit on chemical and biomolecular microbiome research and its impacts on metabolic health, which was recently created by Université Laval and Italy's National Research Council.

To date, studies on obesity have focused primarily on genetic, physiological, and behavioural factors. By integrating a study of the microbiome into conventional approaches, the Chair will expand upon research into this multifactorial disease by shedding light on the complex and subtle mechanisms modulating metabolic health in response to diet.

The Chair will help identify new research avenues, targets, and approaches for maintaining health and preventing the metabolic complications of obesity. The creation of this Chair attests to the reputation for excellence of the scientific research teams at Université Laval and to 60 years of ongoing effort to improve population health.

The research carried out by Vicenzo Di Marzo builds on the extensive expertise of various UL entities, including the Faculty of Medicine, the Faculty of Food and Agriculture Science, the Quebec Heart and Lung Institute Research Centre, renowned for its integrated studies into obesity and chronic social illness, and the Institute of Nutrition and Functional Foods, which is known for its multidisciplinary work on the effects of food on health and the prevention of diet-related chronic illnesses.

Collaboration with the Québec-Italy International Joint Unit will help researchers identify, develop, and formulate new drugs for metabolic health. This new Canada Excellence Research Chair joins 3 other cutting-edge CERC research programs in which Université Laval has been recognized as a leader in Canada:.

These 4 CERCs contribute to the scientific program of Sentinel North. This unprecedented research program on the Canadian North led by Université Laval aims to provide a better understanding of humans, their environment, and the consequences of environmental changes on human health. Skip to main content.

Home Research and Innovation Research units Canada Excellence Research Chair in the Microbiome-Endocannabinoidome Axis in Metabolic Health Vincenzo Di Marzo is developing new therapeutic, nutritional, and medical strategies to maintain health and prevent diseases like obesity.

Background According to the World Health Organization, more than 1. If you are interested in human health, consider furthering your research career with us.

Honours Degrees. Faculty of Health and Medical Sciences. Home Our Research Current: Nutrition and Metabolic Health. Nutrition and Metabolic Health.

Researchers across the faculty are focused on: determining the effects of modifying diet on metabolic health developing strategies to prevent and manage obesity and type 2 diabetes studying the molecular and cellular basis of appetite regulation understanding immune function and pain-sensing in the gut exploring how nutrition interacts with sleep patterns and metabolic disorders investigating metabolism in liver, muscle, fat tissue and bone tissue understanding nutrition in vulnerable populations such as the elderly, and determining the association between nutritional intake and chronic disease conducting longitudinal, large cohort studies to assess associations between diet and chronic diseases.

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