Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans
Open accessAbstract
A BMI in the normal range associates with a decreased risk of cardiometabolic disease and all-cause mortality. However, not all subjects in this BMI range have this low risk. Compared to people who are of normal weight and metabolically healthy, subjects who are of normal weight but metabolically unhealthy (∼20% of the normal weight adult population) have a greater than 3-fold higher risk of all-cause mortality and/or cardiovascular events. Here we address to what extent major risk phenotypes determine metabolic health in lean compared to overweight and obese people and provide support for the existence of a lipodystrophy-like phenotype in the general population. Furthermore, we highlight the molecular mechanisms that induce this phenotype. Finally, we propose strategies as to how this knowledge could be implemented in the prevention and treatment of cardiometabolic diseases in different stages of adiposity in routine clinical practice.
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Skeletal muscle insulin resistance, affecting most persons with obesity, contributes to reduced muscle mass and poor muscle quality, a phenomenon observed in sarcopenic obesity.
“skeletal muscle insulin resistance, affecting most persons with obesity, contributes to reduced muscle mass and poor muscle quality-a phenomenon observed in sarcopenic obesity.18,19”
From Changes in lean body mass with <scp>glucagon‐like peptide</scp> ‐1‐based therapies and mitigation strategies (2024) · cites this paper as [18]
Cites
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629 · see citing works
Lorenz, M. W., Markus, H. S., Bots, M. L., Rosvall, M., & Sitzer, M. (2007) · Circulation · doi:10.1161/circulationaha.106.628875 · Cited by 2,977 · see citing works
Fox, C. S., Massaro, J. M., Hoffmann, U., Pou, K. M., Maurovich-Horvat, P., Liu, C.-Y., Vasan, R. S., Murabito, J. M., Meigs, J. B., Cupples, L. A., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.675355 · Cited by 2,882 · see citing works
Di Angelantonio, E., Bhupathiraju, S. N., Wormser, D., Gao, P., Kaptoge, S., de Gonzalez, A. B., Cairns, B. J., Huxley, R., Jackson, C. L., Joshy, G., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30175-1 · Cited by 2,821 · see citing works
Eckel, R. H., Jakicic, J. M., Ard, J. D., de Jesus, J. M., Miller, N. H., Hubbard, V. S., Lee, I.-M., Lichtenstein, A. H., Loria, C. M., Millen, B. E., et al. (2014) · Circulation · doi:10.1161/01.cir.0000437740.48606.d1 · Cited by 2,261 · see citing works
GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus
Meier, J. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.140 · Cited by 1,311 · see citing works
Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Fabbrini, E., Magkos, F., Mohammed, B. S., Pietka, T., Abumrad, N. A., Patterson, B. W., Okunade, A., & Klein, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904944106 · Cited by 972 · see citing works
Metabolically healthy obesity: Epidemiology, mechanisms, and clinical implications
Stefan, N., Häring, H.-U., Hu, F. B., & Schulze, M. B. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70062-7 · Cited by 857 · see citing works
Self-citationPioglitazone for Diabetes Prevention in Impaired Glucose Tolerance
DeFronzo, R. A., Tripathy, D., Schwenke, D. C., Banerji, M., Bray, G. A., Buchanan, T. A., Clement, S. C., Henry, R. R., Hodis, H. N., Kitabchi, A. E., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1010949 · Cited by 752 · see citing works
The Cardiovascular Biology of Glucagon-like Peptide-1
Drucker, D. J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.009 · Cited by 665 · see citing works
Failure of adipocyte differentiation causes type II diabetes mellitus?
Danforth, E. (2000) · Nature Genetics · doi:10.1038/79111 · Cited by 487 · see citing works
Dubé, J. J., Amati, F., Stefanovic-Racic, M., Toledo, F. G. S., Sauers, S. E., & Goodpaster, B. H. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00769.2007 · Cited by 378 · see citing works
Færch, K., Torekov, S. S., Vistisen, D., Johansen, N. B., Witte, D. R., Jonsson, A., Pedersen, O., Hansen, T., Lauritzen, T., Sandbæk, A., et al. (2015) · Diabetes · doi:10.2337/db14-1751 · Cited by 321 · see citing works
The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis
Fall, T., Hägg, S., Mägi, R., Ploner, A., Fischer, K., Horikoshi, M., Sarin, A.-P., Thorleifsson, G., Ladenvall, C., Kals, M., et al. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001474 · Cited by 203 · see citing works
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Sorted by citations
Eslam, M., Newsome, P. N., Sarin, S. K., Anstee, Q. M., Targher, G., Romero-Gomez, M., Zelber-Sagi, S., Wai-Sun Wong, V., Dufour, J.-F., Schattenberg, J. M., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.03.039 · Cited by 4,472 · see citing works
Blüher, M. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa004 · Cited by 1,090 · see citing works
“In a large BMI-stratified cohort, Stefan et al (20, 23) linked high liver fat content and predominantly abdominal (including visceral) adiposity to MUO, whereas greater insulin sensitivity, better insulin secretion, cardiorespiratory fitness, and lower body subcutaneous fat mass were associated with an MHO phenotype.”
BackgroundHyperglycemia drives intestinal barrier dysfunction and risk for enteric infection
Thaiss, C. A., Levy, M., Grosheva, I., Zheng, D., Soffer, E., Blacher, E., Braverman, S., Tengeler, A. C., Barak, O., Elazar, M., et al. (2018) · Science · doi:10.1126/science.aar3318 · Cited by 942 · see citing works
Stefan, N., Häring, H., & Cusi, K. J. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30154-2 · Cited by 848 · see citing works
Self-citationNAFLD as a Continuum: From Obesity to Metabolic Syndrome and Diabetes
Godoy-Matos, A. F., Silva Júnior, W. S., & Valerio, C. M. (2020) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-020-00570-y · Cited by 643 · see citing works
“Nonetheless, some evidence corroborate that VAT may be a bystander and peripheral SAT may be of utmost importance for metabolic health [35, 36].”
BackgroundObesity and impaired metabolic health in patients with COVID-19
Stefan, N., Birkenfeld, A. L., Schulze, M. B., & Ludwig, D. S. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0364-6 · Cited by 626 · see citing works
“Prediabetes, which is present in 38% of the adult population in the USA, was identified as an important risk factor for CVD and renal disease 5 .”
BackgroundSelf-citationThe Liver as an Endocrine Organ—Linking NAFLD and Insulin Resistance
Watt, M. J., Miotto, P. M., De Nardo, W., & Montgomery, M. K. (2019) · Endocrine Reviews · doi:10.1210/er.2019-00034 · Cited by 615 · see citing works
A Global View of the Interplay between Non-Alcoholic Fatty Liver Disease and Diabetes
Stefan, N., & Cusi, K. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00003-1 · Cited by 593 · see citing works
Self-citationThe obese adipose tissue microenvironment in cancer development and progression
Quail, D. F., & Dannenberg, A. J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0126-x · Cited by 542 · see citing works
Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysis
Mantovani, A., Byrne, C. D., Bonora, E., & Targher, G. (2018) · Diabetes Care · doi:10.2337/dc17-1902 · Cited by 625 · see citing works
“This might also have important implications for future strategies in the prevention and treatment of type 2 diabetes and other cardiometabolic diseases in clinical practice (51,52).”
Causes, consequences, and treatment of metabolically unhealthy fat distribution
Stefan, N. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30110-8 · Cited by 546 · see citing works
Self-citationFrom NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options
Gastaldelli, A., & Cusi, K. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.07.002 · Cited by 455 · see citing works
Vekić, J., Zeljković, A., Stefanović, A., Jelić‐Ivanović, Z., & Spasojević‐Kalimanovska, V. (2018) · Metabolism · doi:10.1016/j.metabol.2018.11.005 · Cited by 623 · see citing works
Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes
Wagner, R., Heni, M., Tabák, A. G., Machann, J., Schick, F., Randrianarisoa, E., Hrabě de Angelis, M., Birkenfeld, A. L., Stefan, N., Peter, A., et al. (2021) · Nature Medicine · doi:10.1038/s41591-020-1116-9 · Cited by 415 · see citing works
Self-citationNeeland, I. J., Linge, J., & Birkenfeld, A. L. (2024) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15728 · Cited by 391 · see citing works
“18,19 Improving insulin sensitivity by weight loss interventions therefore contributes to an adaptive process of muscle mass and function.”
Młynarska, E., Czarnik, W., Kurys, N., Jędraszak, W., Majchrowicz, G., Prusinowski, F., Stabrawa, M., Rysz, J., & Franczyk, B. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031094 · Cited by 419 · see citing works
“Normal-weight patients with a lipodystrophy-like phenotype are also strongly characterized by insulin resistance and impaired secretion of insulin [84].”
InfluentialAzzu, V., Vacca, M., Virtue, S., Allison, M., & Vidal-Puig, A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.054 · Cited by 369 · see citing works
Tumour fatty acid metabolism in the context of therapy resistance and obesity
Hoy, A. J., Nagarajan, S. R., & Butler, L. M. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00388-4 · Cited by 408 · see citing works
Metabolically healthy obesity: the low-hanging fruit in obesity treatment?
Stefan, N., Häring, H., & Schulze, M. B. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30292-9 · Cited by 309 · see citing works
Self-citationMetabolic Syndrome: Past, Present and Future
Lemieux, I., & Despres, J. (2020) · Nutrients · doi:10.3390/nu12113501 · Cited by 272 · see citing works
The role of hepatokines in NAFLD
Stefan, N., Schick, F., Birkenfeld, A. L., Häring, H., & White, M. F. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.01.006 · Cited by 282 · see citing works
Self-citationObesity: A critical risk factor in the COVID ‐19 pandemic
Kwok, S., Adam, S., Ho, J. H., Iqbal, Z., Turkington, P. M., Razvi, S., le Roux, C. W., Soran, H., & Syed, A. A. (2020) · Clinical Obesity · doi:10.1111/cob.12403 · Cited by 254 · see citing works
“This cohort of patients are characterized by a metabolically unhealthy fat distribution with increased visceral adiposity but reduced lower-body fat mass.(36,37) Furthermore, elevated percentage body fat has been”
BackgroundTryptophan Dietary Impacts Gut Barrier and Metabolic Diseases
Taleb, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02113 · Cited by 236 · see citing works
“The prevalence of Western diet-induced metabolic syndrome (MetS) is booming, affecting more than 2 billion people worldwide and accounting for at least 3 million deaths per year (1).”
BackgroundYounes, R., & Bugianesi, E. (2019) · Seminars in Liver Disease · doi:10.1055/s-0038-1677517 · Cited by 235 · see citing works
“22 These key characteristic of MONW are consistent across studies in humans; increased liver fat is probably due to a decreased capacity for storing fat in subcutaneous adiposetissue, coupled with reduced mitochondrial function and increased de novo lipogenesis in the liver.”
Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight
Eslam, M., El‐Serag, H. B., Francque, S., Sarin, S. K., Wei, L., Bugianesi, E., & George, J. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00635-5 · Cited by 246 · see citing works
Nonalcoholic fatty liver disease in adults: current concepts in etiology, outcomes, and management
Marjot, T., Moolla, A., Cobbold, J. F., Hodson, L., & Tomlinson, J. W. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz009 · Cited by 228 · see citing works
Stefan, N., & Schulze, M. B. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00086-4 · Cited by 215 · see citing works
Self-citationChen, G., Arthur, R., Iyengar, N. M., Kamensky, V., Xue, X., Wassertheil-Smoller, S. W., Allison, M., Shadyab, A. H., Wild, R. A., Sun, Y., et al. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz391 · Cited by 242 · see citing works
Li, H., Wu, G., Fang, Q., Zhang, M., Hui, X., Sheng, B., Wu, L., Bao, Y., Li, P., Xu, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02677-9 · Cited by 178 · see citing works
Metabolically healthy obesity: from epidemiology and mechanisms to clinical implications
Schulze, M. B., & Stefan, N. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01008-5 · Cited by 184 · see citing works
“Data from the Tübingen Diabetes Family Study 73 and results from integrative genomic analyses 74 suggest that lipodystrophy-like mechanisms resulting in disproportionate body adipose tissue distribution are strongly related to insulin resistance in the general population.”
Self-citationFactors leading to high morbidity and mortality of COVID ‐19 in patients with type 2 diabetes
Rajpal, A., Rahimi, L., & Ismail‐Beigi, F. (2020) · Journal of Diabetes · doi:10.1111/1753-0407.13085 · Cited by 165 · see citing works
Linge, J., Birkenfeld, A. L., & Neeland, I. J. (2024) · Circulation · doi:10.1161/circulationaha.124.067676 · Cited by 180 · see citing works
“16,17 Improving insulin sensitivity by means of weight loss interventions therefore contributes to an adaptive process of muscle mass and function.”
Metabolic dysfunction and obesity‐related cancer: Beyond obesity and metabolic syndrome
Karra, P., Winn, M., Pauleck, S., Bulsiewicz‐Jacobsen, A., Peterson, L., Coletta, A. M., Doherty, J. A., Ulrich, C. M., Summers, S. A., Gunter, M. J., et al. (2022) · Obesity · doi:10.1002/oby.23444 · Cited by 171 · see citing works
“VAT or adipose tissue expansion and/or distribution independent of BMI could be highly informative (27,74).”
BackgroundMetabolic health in normal-weight and obese individuals
Schulze, M. B. (2018) · Diabetologia · doi:10.1007/s00125-018-4787-8 · Cited by 183 · see citing works
“9 kg/m(2) (the metabolically unhealthy normal-weight [MUHNW] phenotype) [6, 7].”
FTO regulates adipogenesis by controlling cell cycle progression via m6A-YTHDF2 dependent mechanism
Wu, R., Liu, Y., Yao, Y., Zhao, Y., Bi, Z., Jiang, Q. L., Liu, Q. L., Cai, M., Wang, F., Wang, Y., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.08.008 · Cited by 151 · see citing works
Relevance of body composition in phenotyping the obesities
Salmón‐Gómez, L., Catalán, V., Frühbeck, G., & Gómez‐Ambrosi, J. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09796-3 · Cited by 177 · see citing works
Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots
Agrawal, S., Wang, M., Klarqvist, M. D. R., Smith, K., Shin, J. H., Dashti, H., Diamant, N., Choi, S. H., Jurgens, S. J., Ellinor, P. T., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30931-2 · Cited by 151 · see citing works
“As an example, GFAT adjusted for BMI (but not height) associated with rs67807996 (P = 4.1 x 10-14) and rs59985551 (P = 2.1 x 10-13) which have previously been identified as height-associated variants.6,7 A similar phenomenon has previously been noted with waist circumference adjusted for BMI (WCadjBMI) and hip circumf…”
BackgroundMethodInfluentialWatanabe, K., Wilmanski, T. M., Diener, C., Earls, J. C., Zimmer, A., Lincoln, B., Hadlock, J., Lovejoy, J. C., Gibbons, S. M., Magis, A. T., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02248-0 · Cited by 151 · see citing works
Brain insulin sensitivity is linked to adiposity and body fat distribution
Kullmann, S., Valenta, V., Wagner, R., Tschritter, O., Machann, J., Häring, H.-U., Preissl, H., Fritsche, A., & Heni, M. (2020) · Nature Communications · doi:10.1038/s41467-020-15686-y · Cited by 134 · see citing works
Self-citationLin, H., Zhang, L., Zheng, R., & Zheng, Y. (2017) · Medicine · doi:10.1097/md.0000000000008838 · Cited by 153 · see citing works
Soto-Angona, Ó., Anmella, G., Valdés-Florido, M. J., De Uribe-Viloria, N., Carvalho, A. F., Penninx, B. W. J. H., & Berk, M. (2020) · BMC Medicine · doi:10.1186/s12916-020-01713-8 · Cited by 122 · see citing works
Moriconi, D., Masi, S., Rebelos, E., Virdis, A., Manca, M. L., Marco, S. D., Taddei, S., & Nannipieri, M. (2020) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2020.05.009 · Cited by 146 · see citing works
Metabolically healthy obesity: what–s in a name?
Magkos, F. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz133 · Cited by 144 · see citing works
Update on Vascular Cognitive Impairment Associated with Subcortical Small-Vessel Disease
Wallin, A., Román, G. C., Esiri, M. M., Kettunen, P., Svensson, J., Paraskevas, G. P., & Kapaki, E. N. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170803 · Cited by 130 · see citing works
“The metabolic syndrome (METS) includes the clustering of abdominal obesity, insulin resistance, dyslipidemia, and elevated blood pressure [199].”
BackgroundInfluentialAraújo, J., Cai, J., & Stevens, J. (2018) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2018.0105 · Cited by 157 · see citing works
Obesity phenotypes and cardiovascular risk: From pathophysiology to clinical management
Preda, A., Carbone, F., Tirandi, A., Montecucco, F., & Liberale, L. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09813-5 · Cited by 108 · see citing works
“MUNW usually includes older and sedentary individuals [73] with generally a very low amount of gluteo-femoral fat mass compared with the visceral one [74].”
BackgroundMarcondes‐de‐Castro, I. A., Reis‐Barbosa, P. H., Marinho, T. D. S., Águila, M. B., & Mandarim‐de‐Lacerda, C. A. (2023) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16272 · Cited by 103 · see citing works
Coronavirus Disease 2019 (COVID-19) and Nutritional Status: The Missing Link?
Silvério, R., Gonçalves, D. C., Andrade, M. F., & Seelaender, M. C. L. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa125 · Cited by 119 · see citing works
“Assessment of insulin resistance, a robust indicator of altered metabolic health, impaired cardiovascular function, and cardiovascular disease–related mortality, is recommended (59) both in primary care, as well as in the evaluation of the potential risk and prognosis in patients with a positive SARS-CoV-2 test result.”
BackgroundAgrawal, S., Klarqvist, M., Diamant, N., Stanley, T., Ellinor, P., Mehta, N., Philippakis, A. A., Ng, K., Claussnitzer, M., Grinspoon, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35704-5 · Cited by 95 · see citing works
Ji, Y., Yiorkas, A. M., Frau, F., Mook‐Kanamori, D. O., Staiger, H., Thomas, E. L., Atabaki‐Pasdar, N., Campbell, A. I., Tyrrell, J., Jones, S. E., et al. (2018) · Diabetes · doi:10.2337/db18-0708 · Cited by 101 · see citing works
Self-citationKantartzis, K., Fritsche, L., Bombrich, M., Machann, J., Schick, F., Staiger, H., Kunz, I., Schoop, R., Lehn‐Stefan, A., Heni, M., et al. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13268 · Cited by 87 · see citing works
“Diastolic blood pressure (mm Hg) 88 (12) 88 (9) 88 (10) 86 (10) .”
Self-citationChildren With Metabolically Healthy Obesity: A Review
Vuković, R., Santos, T. J. D., Ybarra, M., & Atar, M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00865 · Cited by 98 · see citing works
“There is evidence that increased ratio of the abdominal subcutaneous adipose tissue to total body fat mass is associated with the metabolically unhealthy phenotype, while the increase in the gluteofemoral subcutaneous adipose tissue seems to be positively associated with MHO (90, 91).”
BackgroundMetabolic Obesity in People with Normal Body Weight (MONW)—Review of Diagnostic Criteria
Pluta, W. W., Dudzińska, W., & Lubkowska, A. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19020624 · Cited by 90 · see citing works
“Hepatic insulin resistance is also manifested by increased glycogenolysis and gluconeogenesis, which increases endogenous glucose production and is associated with the development of non-alcoholic fatty liver disease (NAFLD) [20].”
BackgroundWhat role do fat cells play in pancreatic tissue?
Gerst, F., Wagner, R. J., Oquendo, M. B., Siegel-Axel, D. I., Fritsche, A., Heni, M., Staiger, H., Häring, H., & Ullrich, S. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.05.001 · Cited by 90 · see citing works
“Obesity comprises not only increased subcutaneous fat deposition but also visceral fat accumulation [4].”
Self-citationMetabolically Healthy and Unhealthy Normal Weight and Obesity
Stefan, N. (2020) · Endocrinology and Metabolism · doi:10.3803/enm.2020.301 · Cited by 94 · see citing works
“However, as patients with lipodystrophy [7] or a lipodystrophy-like phenotype [8,9] have an increased cardiometabolic risk, it cannot be excluded that particularly a low amount of fat mass in the subcutaneous region may also increase mortality in the general population with a low BMI.”
BackgroundResultSelf-citationObesity and the tumor microenvironment
Olson, O., Quail, D., & Joyce, J. (2017) · Science · doi:10.1126/science.aao5801 · Cited by 76 · see citing works
Cardiometabolic index: a new tool for screening the metabolically obese normal weight phenotype
Liu, X., Wu, Q., Yan, G., Duan, J., chen, Z., Yang, P., Bragazzi, N. L., Lu, Y., & Yuan, H. (2020) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01417-z · Cited by 76 · see citing works
“Previous studies have identified a number of anthropometric, body composition, and metabolic characteristics of MONW persons, of which visceral adiposity and insulin resistance (IR) are pointed out as key features of MONW phenotype [3, 11].”
BackgroundInfluentialDiMenna, F. J., & Arad, A. D. (2018) · BMC Sports Science, Medicine and Rehabilitation · doi:10.1186/s13102-018-0110-8 · Cited by 68 · see citing works
Ozonoff, A., Schaenman, J. M. D., Jayavelu, N. D., Milliren, C. E., Calfee, C. S., Cairns, C. B., Kraft, M., Baden, L. R., Shaw, A. C., Krammer, F., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104208 · Cited by 62 · see citing works
“It could be that impaired metabolic health 20 (characterized by dyslipidemia, and insulin resistance) may be more predictive than BMI per se .”
The Role of Autophagy in White Adipose Tissue Function: Implications for Metabolic Health
Clemente‐Postigo, M., Tinahones, A., Bekay, R. E., Malagón, M. M., & Tinahones, F. J. (2020) · Metabolites · doi:10.3390/metabo10050179 · Cited by 77 · see citing works
Physical Activity and Sedentary Time: Association with Metabolic Health and Liver Fat
Davies, K. A. B., Sprung, V. S., Norman, J. A., Thompson, A., MITCHELL, K. L., HARROLD, J. A., Finlayson, G., Gibbons, C., Wilding, J. P. H., Kemp, G. J., et al. (2019) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001901 · Cited by 72 · see citing works
Brendle, C., Werner, M., Schmadl, M., la Fougère, C., Nikolaou, K., Stefan, N., & Pfannenberg, C. (2018) · Academic Radiology · doi:10.1016/j.acra.2017.09.007 · Cited by 64 · see citing works
Self-citationElevated circulating follistatin associates with an increased risk of type 2 diabetes
Wu, C., Borné, Y., Gao, R., Rodríguez, M. L., Roell, W. C., Wilson, J. M., Regmi, A., Luan, C., Aly, D. M., Peter, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26536-w · Cited by 68 · see citing works
Self-citationVisceral fat: A key mediator of NAFLD development and progression
Bansal, S., Vachher, M., Arora, T. K., Kumar, B., & Burman, A. (2023) · Human Nutrition & Metabolism · doi:10.1016/j.hnm.2023.200210 · Cited by 65 · see citing works
Agius, R., Pace, N. P., & Fava, S. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3725 · Cited by 62 · see citing works
“13–15 Thus, obesity is a metabolically heterogeneous disorder and different obesity ‐ related phenotypes should be considered based on the inter ‐ individual variability in body composition as well as in MH. 16–18 These phenotypes should therefore be regarded as dynamic states.”
BackgroundInfluentialInsulin and cancer: a tangled web
Leitner, B. P., Siebel, S., Akingbesote, N. D., Zhang, X., & Perry, R. J. (2022) · Biochemical Journal · doi:10.1042/bcj20210134 · Cited by 76 · see citing works
Metabolically healthy obesity and metabolically obese normal weight: a review
Gómez‐Zorita, S., Queralt, M., Vicente, M. Á., González, M. A., & Portillo, M. P. (2021) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-020-00781-x · Cited by 75 · see citing works
Non-alcoholic fatty liver disease in non-obese individuals: the impact of metabolic health
Eslam, M., Fan, J., & Méndez‐Sánchez, N. (2020) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(20)30090-x · Cited by 68 · see citing works
Visceral adiposity, inflammation, and hippocampal function in obesity
Stranahan, A. M. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108920 · Cited by 63 · see citing works
Cho, Y. K., Kang, Y. M., Yoo, J. H., Lee, J., Park, J., Lee, W. J., Kim, Y., & Jung, C. H. (2019) · Metabolism · doi:10.1016/j.metabol.2019.05.002 · Cited by 69 · see citing works
Sánchez‐González, C., Nuevo‐Tapioles, C., Martín, J. C. H., Pereira, M. P., Sanz, S. S., de Molina, A. R., Cuezva, J. M., & Formentini, L. (2020) · The EMBO Journal · doi:10.15252/embj.2019103812 · Cited by 54 · see citing works
“Obesity is a complex chronic condition that affects all organ systems and increases the rate of premature mortality (Spiegelman & Flier, 2001; Stefan et al , 2017).”
Update on Obesity and Cardiovascular Risk: From Pathophysiology to Clinical Management
Gallo, G., Desideri, G., & Savoia, C. (2024) · Nutrients · doi:10.3390/nu16162781 · Cited by 52 · see citing works
“These include increased WC, WHiR, and WHtR [75].”
BackgroundZhong, P., Tan, S., Zhu, Z., Zhu, Z., Liang, Y., Huang, W., & Wang, W. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3707 · Cited by 61 · see citing works
“21,22,36 A prospective cohort study found that higher trunk fat was a favourable factor, while higher leg fat was unfavourable for reducing CVD risks.”
BackgroundSARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner
Saccon, T. D., Mousovich‐Neto, F., Ludwig, R. G., Carregari, V. C., Souza, A. B. D. A., dos Passos, A. S. C., Martini, M. C., Barbosa, P. P., de Souza, G. F., Muraro, S. P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33218-8 · Cited by 65 · see citing works
Metabolically healthy and unhealthy obesity in erectile dysfunction and male infertility
Rastrelli, G., Lotti, F., Reisman, Y., Sforza, A., Maggi, M., & Corona, G. (2019) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2019.1657827 · Cited by 62 · see citing works
“According to these results, MUHNW subjects, as compared to the other phenotypes (MHO and MUHO), were characterized by insulin secretion failure and insulin resistance as well as an increased carotid intima-media thickness [38] Table 1.”
BackgroundResultInfluentialZhang, Y., Wang, Q., Chen, Y.-S., Shen, C., & Xu, C. (2020) · International Journal of Endocrinology · doi:10.1155/2020/5953461 · Cited by 60 · see citing works
“nonobese individuals are metabolically unhealthy and have unfavorable metabolic profiles [33].”
BackgroundStorz, C., Heber, S. D., Rospleszcz, S., Machann, J., Sellner, S., Nikolaou, K., Lorbeer, R., Gatidis, S., Elser, S., Peters, A., et al. (2018) · British Journal of Radiology · doi:10.1259/bjr.20170808 · Cited by 52 · see citing works
Bae, H., Hong, K. Y., Lee, C.-K., Jang, C., Lee, S.-J., Choe, K., Offermanns, S., He, Y., Lee, H. J., & Koh, G. Y. (2020) · Nature Communications · doi:10.1038/s41467-020-16795-4 · Cited by 52 · see citing works
García‐García, I., Michaud, A., Jurado, M. Á., Dagher, A., & Morys, F. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09706-5 · Cited by 53 · see citing works
“For instance, some individuals suffer from obesity-associated comorbidities (such as insulin resistance or low grade inflammation) despite having a BMI categorized as normal-weight [5].”
BackgroundObesity and Pregnancy, the Perfect Metabolic Storm
Corrales, P., Vidal-Puig, A., & Medina-Gómez, G. (2021) · European Journal of Clinical Nutrition · doi:10.1038/s41430-021-00914-5 · Cited by 51 · see citing works
for the Metabolic Syndrome Study Group, Elías-López, D., Vargas‐Vázquez, A., Mehta, R., Bautista, I. C., Razo-Olvera, F. M. D., Gómez‐Velasco, D., Valdés, P. A., & Aguilar-Salinas, C. A. (2021) · BMC Endocrine Disorders · doi:10.1186/s12902-021-00754-1 · Cited by 62 · see citing works
Gudan, A., Kozłowska‐Petriczko, K., Wunsch, E., Bodnarczuk, T., & Stachowska, E. (2023) · Nutrients · doi:10.3390/nu15061323 · Cited by 48 · see citing works
“Disproportionate body fat distribution (especially visceral adiposity) and adipose tissue dysfunction play a pivotal role in the pathogenesis of IR and NAFLD in lean phenotype [11,12].”
BackgroundVerdú, E., Homs, J., & Boadas‐Vaello, P. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182413333 · Cited by 54 · see citing works
Semmler, G., Wernly, S., Bachmayer, S., Wernly, B., Schwenoha, L., Huber-Schönauer, U., Stickel, F., Niederseer, D., Aigner, E. S., & Datz, C. (2021) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000326 · Cited by 54 · see citing works
Lipodystrophic Nonalcoholic Fatty Liver Disease Induced by Immune Checkpoint Blockade
Eigentler, T., Lomberg, D., Machann, J., & Stefan, N. (2020) · Annals of Internal Medicine · doi:10.7326/l19-0635 · Cited by 49 · see citing works
“For example, although NAFLD is usually found in obese patients, it also is found in about 18% of normalweight persons with a high cardiometabolic risk (3).”
BackgroundSelf-citationRandrianarisoa, E., Lehn‐Stefan, A., Hieronimus, A., Rietig, R., Fritsche, A., Machann, J., Balletshofer, B. M., Häring, H., Stefan, N., & Rittig, K. (2019) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.47274 · Cited by 50 · see citing works
Self-citationWillmes, D. M., Kurzbach, A., Henke, C., Schumann, T., Zahn, G., Heifetz, A., Jordan, J., Helfand, S. L., & Birkenfeld, A. L. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.10.003 · Cited by 45 · see citing works
Akbari, P., Sosina, O. A., Bovijn, J., Landheer, K., Nielsen, J. B., Kim, M., Aykul, S., De, T., Haas, M. E., Hindy, G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32398-7 · Cited by 56 · see citing works
Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms
Pánico, P., Velasco, M., Salazar, A. M., Picones, A., Ortiz-Huidobro, R. I., Guerrero‐Palomo, G., Salgado-Bernabé, M. E., Ostrosky‐Wegman, P., & Hiriart, M. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.878280 · Cited by 53 · see citing works
Molli, A. E. I., Steinhardt, A. P., López, A. P., González, C. D., Vilarino, J. F., Frechtel, G. D., & Cerrone, G. E. (2017) · PLoS ONE · doi:10.1371/journal.pone.0190528 · Cited by 47 · see citing works
Tanabe, H., Masuzaki, H., & Shimabukuro, M. (2021) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2021.109067 · Cited by 59 · see citing works
Gesteiro, E., Megía, A., Guadalupe‐Grau, A., Fernández‐Veledo, S., Vendrell, J. J., & González‐Gross, M. (2021) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2021.05.022 · Cited by 51 · see citing works
Zheng, Q., Lin, W., Liu, C.-G., Zhou, Y., Chen, T.-H., Zhang, L.-Q., Zhang, X.-H., Yu, S., Wu, Q., Jin, Z., et al. (2020) · BMC Public Health · doi:10.1186/s12889-020-08630-8 · Cited by 46 · see citing works
“Obese individuals with an “apple shape,” hypertrophy, or metabolic abnormality have higher risk for adverse outcomes [4, 5].”
BackgroundRolle-Kampczyk, U. E., Gebauer, S., Haange, S., Schubert, K. A., Kern, M., Moulla, Y., Dietrich, A., Schön, M. R., Klöting, N., von Bergen�, M., et al. (2020) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2020.142458 · Cited by 51 · see citing works
Abolnezhadian, F., Hosseini, S. A., Alipour, M., Zakerkish, M., Cheraghian, B., Ghandil, P., & Cheraghpour, M. (2020) · Vascular Health and Risk Management · doi:10.2147/vhrm.s251927 · Cited by 52 · see citing works
Sandoval, V., Femenias, A., Martínez‐Garza, Ú., Sanz‐Lamora, H., Castagnini, J. M., Quifer‐Rada, P., Lamuela-Raventós, R. M., Marrero, P. F., Haro, D., & Relat, J. (2019) · Antioxidants · doi:10.3390/antiox8090360 · Cited by 46 · see citing works
Tale of two Indians: Heterogeneity in type 2 diabetes pathophysiology
Staimez, L. R., Deepa, M., Ali, M. K., Mohan, V., Hanson, R. L., & Narayan, K. M. V. (2019) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3192 · Cited by 46 · see citing works
“FIGURE 2 Hypothesis: Heterogeneous phenotypes of type 2 diabetes r resistance and adiposity as observed in Pima Indians, and Phenotype 2b, c functional capacity of the pancreatic beta‐cells, as observed in Asian India normal weight subjects were metabolically unhealthy, and the most prevalent risk phenotype was insuli…”
BackgroundAdipose tissue and the physiologic underpinnings of metabolic disease
O’Rourke, R. W. (2018) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2018.07.032 · Cited by 53 · see citing works
“the prevalence of metabolically obese but normal weight among patients with normal BMI ranges from 20% in white people to up to 40% in South Asian people [32,33].”
BackgroundPhysiopathology of Lifestyle Interventions in Non-Alcoholic Fatty Liver Disease (NAFLD)
Carneros, D., López‐Lluch, G., & Bustos, M. (2020) · Nutrients · doi:10.3390/nu12113472 · Cited by 47 · see citing works
Blüher, M., & Laufs, U. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz411 · Cited by 40 · see citing works
- Authors
- Stefan, N., Schick, F., & Häring, H.-U.
- Affiliations
- Helmholtz Munich (DE)
- Corresponding author
- Stefan, Norbert
- Häring, Hans-Ulrich
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 26
- Issue
- 2
- Pages
- 292-300
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2741982109
- Cited by
- 575
- References
- 0
- Citations by year
- 2026: 50 · 2025: 53 · 2024: 58 · 2023: 60 · 2022: 99 · 2021: 76 · 2020: 88 · 2019: 40 · 2018: 40 · 2017: 10
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (KFO 114, STE 1096/1-3)
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- metabolically unhealthy normal weight, metabolic health, cardiometabolic disease, all-cause mortality, cardiovascular risk, adiposity, risk phenotypes, molecular mechanisms, disease prevention, treatment options
- MeSH terms
- Female, Heart Diseases, Humans, Male, Metabolic Diseases, Risk Factors, Body Mass Index, Adiposity
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