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Physiological and Lifestyle Traits of Metabolic Dysfunction in the Absence of Obesity


Purpose of Review

Individuals with metabolically unhealthy normal weight (MUNW) have an adverse cardiometabolic risk factor profile in the absence of excess body weight, and increased risk for diabetes and heart disease. We critically review some physiological traits and lifestyle characteristics of the MUNW phenotype.

Recent Findings

The prevalence of MUNW varies considerably around the world and among ethnicities, partly because of different definitions; on average, this phenotype affects about ~ 30% of normal weight persons globally. Most studies have recruited MUNW subjects who, although within the normal weight range, are significantly “more obese” than their metabolically healthy lean peers (greater body mass index or total body fat); hence one cannot ascertain whether observed differences are true traits of the MUNW phenotype of simply secondary to greater relative adiposity within the normal range. Carefully matched studies have indicated that MUNW can exist in the absence of excess total body fat. These subjects have a preferential accumulation of fat in the upper body (abdominal subcutaneous and visceral adipose tissues) and the liver, but not skeletal muscle; perhaps surprisingly, this predominantly “android” fat distribution does not translate into increased waist circumference. The MUNW phenotype is associated with lower aerobic fitness and muscle mass and strength, but whether this is simply due to inadequate regular physical activity is not entirely clear. Likewise, no consistent associations have been found between any dietary factors and the development of MUNW phenotype, but diet-induced modest weight loss facilitates its resolution.


Delineating the mechanisms leading to metabolic dysfunction in the absence of increased body weight and body fat will likely reveal important targets for improving metabolic health and eventually for reducing the burden of cardiometabolic disease, not only in individuals with normal body weight but also in people with obesity.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Brussels: International Diabetes Federation; 2019.

    Google Scholar 

  2. 2.

    Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 1994;17:961–9.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122:481–6.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med. 1999;341:427–34.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Eckel N, Muhlenbruch K, Meidtner K, Boeing H, Stefan N, Schulze MB. Characterization of metabolically unhealthy normal-weight individuals: risk factors and their associations with type 2 diabetes. Metabolism. 2015;64:862–71.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Wang L, Gao P, Zhang M, Huang Z, Zhang D, Deng Q, et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA. 2017;317:2515–23.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Kuwahara K, Honda T, Nakagawa T, Yamamoto S, Hayashi T, Mizoue T. Body mass index trajectory patterns and changes in visceral fat and glucose metabolism before the onset of type 2 diabetes. Sci Rep. 2017;7:43521.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.•

    Gujral UP, Mohan V, Pradeepa R, Deepa M, Anjana RM, Narayan KM. Ethnic differences in the prevalence of diabetes in underweight and normal weight individuals: the CARRS and NHANES studies. Diabetes Res Clin Pract. 2018;146:34–40. A large cross-sectional survey of type 2 diabetes incidence in normal-weight Asian Indian and White men and women, which demonstrates 2-fold greater prevalence in men and 4-fold greater prevalence in Asian Indians.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.••

    Zhu Y, Sidell MA, Arterburn D, Daley MF, Desai J, Fitzpatrick SL. et al, Racial/ethnic disparities in the prevalence of diabetes and prediabetes by BMI: Patient Outcomes Research To Advance Learning (PORTAL) multisite cohort of adults in the U.S. Diabetes Care. 2019;42:2211–9. This study determined the prevalence of diabetes and prediabetes in almost 5 million US men and women, included Whites and various racial/ethnic minorities, as well as all BMI strata, and found that minorities had a higher burden of diabetes and prediabetes at lower BMI values than Whites, suggesting the role of factors other than obesity in diabetes and prediabetes risk.

    Article  Google Scholar 

  10. 10.••

    Chan Z, Chooi YC, Ding C, Choo J, Sadananthan SA, Michael N, et al. Sex differences in glucose and fatty acid metabolism in Asians who are nonobese. J Clin Endocrinol Metab. 2019;104:127–36. In this study, body composition, fat distribution, physical fitness, and glucose and fatty acid metabolism were evaluated in normal-weight Asian men and women. There were no sex differences in ectopic fat deposition (liver and muscle), postprandial insulin secretion and clearance rates, and muscle insulin sensitivity (insulin-mediated glucose uptake) but adipose tissue insulin sensitivity (meal-induced suppression of fatty acid concentrations) was greater in women than in men.

    Article  PubMed  Google Scholar 

  11. 11.

    Ruderman NB, Schneider SH, Berchtold P. The "metabolically-obese," normal-weight individual. Am J Clin Nutr. 1981;34:1617–21.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. The metabolically obese, normal-weight individual revisited. Diabetes. 1998;47:699–713.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    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. 2015;47:839–45.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Benziger CP, Bernabe-Ortiz A, Gilman RH, Checkley W, Smeeth L, Malaga G, et al. Metabolic abnormalities are common among south American Hispanics subjects with normal weight or excess body weight: the CRONICAS cohort study. PLoS One. 2015;10:e0138968.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Durward CM, Hartman TJ, Nickols-Richardson SM. All-cause mortality risk of metabolically healthy obese individuals in NHANES III. J Obes. 2012;2012:460321.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16.••

    Caleyachetty R, Thomas GN, Toulis KA, Mohammed N, Gokhale KM, Balachandran K, et al. Metabolically healthy obese and incident cardiovascular disease events among 3.5 million men and women. J Am Coll Cardiol. 2017;70:1429–37. A prospective study (~5.5 years) in a cohort of 3.5 million adults that evaluated the relationship between cardiometabolic abnormalities and risk of cardiovascular disease. It was found that there is an almost dose-response relationship between the number of risk factors and risk of cardiovascular disease across all BMI strata, including normal-weight subjects.

    Article  PubMed  Google Scholar 

  17. 17.

    Ding C, Chan Z, Magkos F. Lean, but not healthy: the 'metabolically obese, normal-weight' phenotype. Curr Opin Clin Nutr Metab Care. 2016;19:408–17.

    CAS  Article  PubMed  Google Scholar 

  18. 18.•

    Magkos F. Metabolically healthy obesity: what's in a name? Am J Clin Nutr. 2019;110:533–9. An updated review on metabolically healthy obesity that concludes that factors involved in the presence or absence of metabolic disease in obesity are largely similar to those in normal-weight persons.

    Article  PubMed  Google Scholar 

  19. 19.

    Heianza Y, Arase Y, Tsuji H, Fujihara K, Saito K, Hsieh SD, et al. Metabolically healthy obesity, presence or absence of fatty liver, and risk of type 2 diabetes in Japanese individuals: Toranomon hospital health management center study 20 (TOPICS 20). J Clin Endocrinol Metab. 2014;99:2952–60.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Luo D, Liu F, Li X, Yin D, Lin Z, Liu H, et al. Comparison of the effect of 'metabolically healthy but obese' and 'metabolically abnormal but not obese' phenotypes on development of diabetes and cardiovascular disease in Chinese. Endocrine. 2015;49:130–8.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Yoo HJ, Hwang SY, Hong HC, Choi HY, Seo JA, Kim SG, et al. Association of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis. Atherosclerosis. 2014;234:218–23.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Haghighatdoost F, Amini M, Aminorroaya A, Abyar M, Feizi A. Different metabolic/obesity phenotypes are differentially associated with development of prediabetes in adults: results from a 14-year cohort study. World J Diabetes. 2019;10:350–61.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.••

    Lin H, Zhang L, Zheng R, Zheng Y. The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA-compliant article. Medicine (Baltimore). 2017;96:e8838. A systematic review and meta-analysis that exemplifies the transient nature of metabolic health in people with normal weight and obesity. About 1-in-4 metabolically healthy normal weight subjects and 1-in-2 metabolically healthy obese subjects will develop ≥1 metabolic abnormality during ~10 years of natural follow-up.

    Article  Google Scholar 

  24. 24.

    Kim JA, Kim DH, Kim SM, Park YG, Kim NH, Baik SH, et al. Impact of the dynamic change of metabolic health status on the incident type 2 diabetes: A nationwide population-based cohort study. Endocrinol Metab (Seoul). 2019;34:406–14.

    Article  Google Scholar 

  25. 25.•

    Gujral UP, Narayan KMV. Diabetes in normal-weight individuals: High susceptibility in nonwhite populations. Diabetes Care. 2019;42:2164–6. An up-to-date commentary on the importance of understanding the pathophysiology of type 2 diabetes in normal weight individuals.

    Article  PubMed  Google Scholar 

  26. 26.

    Indulekha K, Surendar J, Anjana RM, Geetha L, Gokulakrishnan K, Pradeepa R, et al. Metabolic obesity, adipocytokines, and inflammatory markers in Asian Indians--CURES-124. Diabetes Technol Ther. 2015;17:134–41.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Di Renzo L, Galvano F, Orlandi C, Bianchi A, Di Giacomo C, La Fauci L, et al. Oxidative stress in normal-weight obese syndrome. Obesity (Silver Spring). 2010;18:2125–30.

    CAS  Article  Google Scholar 

  28. 28.

    Katsuki A, Sumida Y, Urakawa H, Gabazza EC, Murashima S, Maruyama N, et al. Increased visceral fat and serum levels of triglyceride are associated with insulin resistance in Japanese metabolically obese, normal weight subjects with normal glucose tolerance. Diabetes Care. 2003;26:2341–4.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Kim TN, Park MS, Yang SJ, Yoo HJ, Kang HJ, Song W, et al. Body size phenotypes and low muscle mass: the Korean sarcopenic obesity study (KSOS). J Clin Endocrinol Metab. 2013;98:811–7.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Choi J, Se-Young O, Lee D, Tak S, Hong M, Park SM, et al. Characteristics of diet patterns in metabolically obese, normal weight adults (Korean National Health and nutrition examination survey III, 2005). Nutr Metab Cardiovasc Dis. 2012;22:567–74.

    CAS  Article  PubMed  Google Scholar 

  31. 31.•

    Ojwang AA, Smuts CM, Zec M, Wentzel-Viljoen E, Kruger IM, Kruger HS. Comparison of dietary and plasma phospholipid fatty acids between normal weight and overweight black South Africans according to metabolic health: The PURE study. Prostaglandins Leukot Essent Fatty Acids. 2019:102039. One of the few studies conducted in Africa on the physiological and metabolic traits of metabolically unhealthy normal weight.

  32. 32.•

    Lu YC, Lin YC, Yen AM, Chan WP. Dual-energy X-ray absorptiometry-assessed adipose tissues in metabolically unhealthy normal weight Asians. Sci Rep. 2019;9:17698. A study using dual x-ray absorptiometry in ~3250 normal weight men and women that demonstrates almost linearly increasing odds for metabolically unhealthy normal weight with increasing values for various adiposity indexes within the normal BMI range.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    De Lorenzo A, Del Gobbo V, Premrov MG, Bigioni M, Galvano F, Di Renzo L. Normal-weight obese syndrome: early inflammation? Am J Clin Nutr. 2007;85:40–5.

    Article  PubMed  Google Scholar 

  34. 34.

    Di Renzo L, Del Gobbo V, Bigioni M, Premrov MG, Cianci R, De Lorenzo A. Body composition analyses in normal weight obese women. Eur Rev Med Pharmacol Sci. 2006;10:191–6.

    PubMed  Google Scholar 

  35. 35.

    Dvorak RV, DeNino WF, Ades PA, Poehlman ET. Phenotypic characteristics associated with insulin resistance in metabolically obese but normal-weight young women. Diabetes. 1999;48:2210–4.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Succurro E, Marini MA, Frontoni S, Hribal ML, Andreozzi F, Lauro R, et al. Insulin secretion in metabolically obese, but normal weight, and in metabolically healthy but obese individuals. Obesity (Silver Spring). 2008;16:1881–6.

    CAS  Article  Google Scholar 

  37. 37.

    Wurtz P, Wang Q, Kangas AJ, Richmond RC, Skarp J, Tiainen M, et al. Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change. PLoS Med. 2014;11:e1001765.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Deurenberg-Yap M, Chew SK, Lin VF, Tan BY, van Staveren WA, Deurenberg P. Relationships between indices of obesity and its co-morbidities in multi-ethnic Singapore. Int J Obes Relat Metab Disord. 2001;25:1554–62.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    St-Onge MP, Janssen I, Heymsfield SB. Metabolic syndrome in normal-weight Americans: new definition of the metabolically obese, normal-weight individual. Diabetes Care. 2004;27:2222–8.

    Article  PubMed  Google Scholar 

  40. 40.

    Ni Mhurchu C, Parag V, Nakamura M, Patel A, Rodgers A, Lam TH, et al. Body mass index and risk of diabetes mellitus in the Asia-Pacific region. Asia Pac J Clin Nutr. 2006;15:127–33.

    PubMed  Google Scholar 

  41. 41.

    Romero-Corral A, Somers VK, Sierra-Johnson J, Korenfeld Y, Boarin S, Korinek J, et al. Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J. 2010;31:737–46.

    Article  PubMed  Google Scholar 

  42. 42.

    Hyun YJ, Koh SJ, Chae JS, Kim JY, Kim OY, Lim HH, et al. Atherogenecity of LDL and unfavorable adipokine profile in metabolically obese, normal-weight woman. Obesity (Silver Spring). 2008;16:784–9.

    CAS  Article  Google Scholar 

  43. 43.

    Conus F, Allison DB, Rabasa-Lhoret R, St-Onge M, St-Pierre DH, Tremblay-Lebeau A, et al. Metabolic and behavioral characteristics of metabolically obese but normal-weight women. J Clin Endocrinol Metab. 2004;89:5013–20.

    CAS  Article  PubMed  Google Scholar 

  44. 44.••

    Ding C, Chan Z, Chooi YC, Choo J, Sadananthan SA, Chang A, et al. Regulation of glucose metabolism in nondiabetic, metabolically obese normal-weight Asians. Am J Physiol Endocrinol Metab. 2018;314:E494–502. One of the few studies that evaluated body composition and metabolic function in metabolically healthy and unhealthy Asians matched for age, sex, BMI and total body fat. It was found that the MUNW phenotype is associated with accumulation of fat in the intra-abdominal area and the liver, profound insulin resistance, but also a robust beta-cell insulin secretion response that compensates for insulin resistance and helps maintain glucose homeostasis.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Takeno K, Tamura Y, Kawaguchi M, Kakehi S, Watanabe T, Funayama T, et al. Relation between insulin sensitivity and metabolic abnormalities in Japanese men with BMI of 23-25 kg/m2. J Clin Endocrinol Metab. 2016;101:3676–84.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Fontana L, Klein S, Holloszy JO. Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production. Age (Dordr). 2010;32:97–108.

    CAS  Article  Google Scholar 

  47. 47.

    Wang XL, Chang XY, Tang XX, Chen ZG, Zhou T, Sun K. Peripheral invariant natural killer T cell deficiency in metabolically unhealthy but normal weight versus metabolically healthy but obese individuals. J Int Med Res. 2016;44:1272–82.

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Gutierrez-Repiso C, Soriguer F, Rojo-Martinez G, Garcia-Fuentes E, Valdes S, Goday A, et al. Variable patterns of obesity and cardiometabolic phenotypes and their association with lifestyle factors in the study. Nutr Metab Cardiovasc Dis. 2014;24:947–55.

    Article  PubMed  Google Scholar 

  49. 49.•

    Kim HY, Kim JK, Shin GG, Han JA, Kim JW. Association between abdominal obesity and cardiovascular risk factors in adults with normal body mass index: Based on the sixth Korea National Health and Nutrition Examination Survey. J Obes Metab Syndr. 2019;28:262–70. A study in normal weight Asians that demonstrates that increasing BMI within the normal weight range is associated with increasing waist circumference.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Badoud F, Perreault M, Zulyniak MA, Mutch DM. Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals. FASEB J. 2015;29:748–58.

    CAS  Article  PubMed  Google Scholar 

  51. 51.•

    Wei Y, Wang J, Han X, Yu C, Wang F, Yuan J, et al. Metabolically healthy obesity increased diabetes incidence in a middle-aged and elderly Chinese population. Diabetes Metab Res Rev. 2020;36:e3202. A study in ~18000 Asians demonstrating that metabolically unhealthy normal weight is associated with increased risk of diabetes, not only compared with metabolically healthy normal weight but also compared with metabolically healthy obesity.

    CAS  Article  PubMed  Google Scholar 

  52. 52.••

    Stefan N, Schick F, Haring HU. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab. 2017;26:292–300. A comprehensive phenotyping of metabolic health and disease in normal weight, overweight and obese Caucasians. Intra-abdominal fat, subcutaneous abdominal fat, and liver fat were associated with metabolic disease, whereas aerobic fitness, leg fat, insulin sensitivity and insulin secretion were associated with metabolic health, in all BMI strata and both sexes.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Furukawa Y, Tamura Y, Takeno K, Funayama T, Kaga H, Suzuki R, et al. Impaired peripheral insulin sensitivity in non-obese Japanese patients with type 2 diabetes mellitus and fatty liver. J Diabetes Investig. 2018;9:529–35.

    CAS  Article  Google Scholar 

  54. 54.•

    Chan Z, Ding C, Chooi YC, Choo J, Sadananthan SA, Sasikala S, et al. Ectopic fat and aerobic fitness are key determinants of glucose homeostasis in nonobese Asians. Eur J Clin Invest. 2019;49:e13079. A cross-sectional study in 60 normal weight Asian men and women that evaluates the relationships between body fat distribution, ectopic fat, aerobic fitness, muscular strength, and key components of metabolic health and disease (insulin-mediated glucose disposal and pancreatic insulin secretion); aerobic fitness emerged as a major determinant of metabolic function.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Godoy-Matos AF, Valerio CM, Moreira RO, Momesso DP, Bittencourt LK. Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy. Diabetol Metab Syndr. 2018;10:71.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56.•

    Akinci B, Meral R, Oral EA. Phenotypic and genetic characteristics of lipodystrophy: Pathophysiology, metabolic abnormalities, and comorbidities. Curr Diab Rep. 2018;18:143. An update on the genetics and metabolic abdnormalities of the various generalized and partial lipodystrophy syndromes.

    CAS  Article  PubMed  Google Scholar 

  57. 57.•

    Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet. 2017;49:17–26. A multi-trait GWAS that identified several genetic loci associated with an insulin resistant phenotype (increased fasting insulin and triglyceride concentrations and decreased HDL cholesterol concentration) in the absence of obesity; these loci were strongly linked with decreased accumulation of fat in the lower body (legs).

    CAS  Article  PubMed  Google Scholar 

  58. 58.•

    Chen GC, Arthur R, Iyengar NM, Kamensky V, Xue X, Wassertheil-Smoller S, et al. Association between regional body fat and cardiovascular disease risk among postmenopausal women with normal body mass index. Eur Heart J. 2019;40:2849–55. A prospective study (~18 years) in a cohort of ~2700 normal weight women showing that truncal fat is associated positively with CVD risk, whereas leg fat is associated negatively with CVD risk.

    Article  PubMed  PubMed Central  Google Scholar 

  59. 59.•

    Cuthbertson DJ, Steele T, Wilding JP, Halford JC, Harrold JA, Hamer M, et al. What have human experimental overfeeding studies taught us about adipose tissue expansion and susceptibility to obesity and metabolic complications? Int J Obes (Lond). 2017;41:853–65. A review of the "adipose tissue expandability theory" which postulates that inability of subcutaneous adipose tissue (particularly in the lower body) to expand and store the excess calories results in a channeling and storage of fat in visceral adipose tissue and key metabolic organs (e.g. liver, muscle, pancreas).

    CAS  Article  Google Scholar 

  60. 60.•

    Samouda H, Ruiz-Castell M, Karimi M, Bocquet V, Kuemmerle A, Chioti A, et al. Metabolically healthy and unhealthy weight statuses, health issues and related costs: Findings from the 2013–2015 European Health Examination Survey in Luxembourg. Diabetes Metab. 2019;45:140–51. An analysis indicating that development of a metabolically unhealthy phenotype at all levels of BMI (normal weight, overweight, and obesity) is associated with several health issues as well as higher healthcare and loss-of-productivity costs.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Lee K. Metabolically obese but normal weight (MONW) and metabolically healthy but obese (MHO) phenotypes in Koreans: characteristics and health behaviors. Asia Pac J Clin Nutr. 2009;18:280–4.

    PubMed  Google Scholar 

  62. 62.

    Guerrero-Romero F, Aradillas-Garcia C, Simental-Mendia LE, Torres-Rodriguez ML, Mendoza Ede L, Rosales-Cervantes J, et al. Biochemical characteristics and risk factors for insulin resistance at different levels of obesity. Pediatrics. 2013;131:e1211–7.

    Article  PubMed  Google Scholar 

  63. 63.

    Molero-Conejo E, Morales LM, Fernandez V, Raleigh X, Gomez ME, Semprun-Fereira M, et al. Lean adolescents with increased risk for metabolic syndrome. Arch Latinoam Nutr. 2003;53:39–46.

    PubMed  Google Scholar 

  64. 64.

    Yaghootkar H, Scott RA, White CC, Zhang W, Speliotes E, Munroe PB, et al. Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes. 2014;63:4369–77.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. 65.•

    Huang LO, Loos RJF, Kilpelainen TO. Evidence of genetic predisposition for metabolically healthy obesity and metabolically obese normal weight. Physiol Genomics. 2018;50:169–78. A review of the results from genomic studies that unravel the genetic aspects of the mechanisms that underpin metabolically unhealthy normal weight and metabolically healthy obesity.

    CAS  Article  PubMed  Google Scholar 

  66. 66.•

    Viitasalo A, Pitkanen N, Pahkala K, Lehtimaki T, Viikari JSA, Raitakari O, et al. Increase in adiposity from childhood to adulthood predicts a metabolically obese phenotype in normal-weight adults. Int J Obes (Lond). 2019. A longitudinal study of ~1200 Finns who were followed up from childhood to adulthood, which identified the increase in BMI as the strongest predictor of metabolically unhealthy normal weight phenotype in adulthood.

    Article  Google Scholar 

  67. 67.

    Ramirez-Velez R, Correa-Bautista JE, Lobelo F, Izquierdo M, Alonso-Martinez A, Rodriguez-Rodriguez F, et al. High muscular fitness has a powerful protective cardiometabolic effect in adults: influence of weight status. BMC Public Health. 2016;16:1012.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Park YM, Fung TT, Steck SE, Zhang J, Hazlett LJ, Han K, et al. Diet quality and mortality risk in metabolically obese normal-weight adults. Mayo Clin Proc. 2016;91:1372–83.

    Article  PubMed  Google Scholar 

  69. 69.

    Hashemipour S, Esmailzadehha N, Mohammadzadeh M, Ziaee A. Association of meat and dairy consumption with normal weight metabolic obesity in men: the Qazvin metabolic diseases study. Eat Weight Disord. 2016;21:419–25.

    Article  PubMed  Google Scholar 

  70. 70.

    Rotar O, Boyarinova M, Orlov A, Solntsev V, Zhernakova Y, Shalnova S, et al. Metabolically healthy obese and metabolically unhealthy non-obese phenotypes in a Russian population. Eur J Epidemiol. 2017;32:251–4.

    Article  PubMed  Google Scholar 

  71. 71.•

    Martinez-Gomez D, Ortega FB, Hamer M, Lopez-Garcia E, Struijk E, Sadarangani KP, et al. Physical activity and risk of metabolic phenotypes of obesity: A prospective Taiwanese cohort study in more than 200,000 adults. Mayo Clin Proc. 2019;94:2209–19. A large study in Asians that evaluates the role of physical activity patterns in the interconversion between phenotypes of metabolic health and adiposity.

    Article  PubMed  Google Scholar 

  72. 72.

    Kimokoti RW, Judd SE, Shikany JM, Newby PK. Metabolically healthy obesity is not associated with food intake in white or black men. J Nutr. 2015;145:2551–61.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Park YM, Steck SE, Fung TT, Zhang J, Hazlett LJ, Han K, et al. Mediterranean diet, dietary approaches to stop hypertension (DASH) style diet, and metabolic health in U.S. adults. Clin Nutr. 2017;36:1301–9.

    Article  PubMed  Google Scholar 

  74. 74.

    Pereira DL, Juvanhol LL, Silva DC, Longo GZ. Dietary patterns and metabolic phenotypes in Brazilian adults: a population-based cross-sectional study. Public Health Nutr. 2019;22:3377–83.

    Article  PubMed  Google Scholar 

  75. 75.

    Kimokoti RW, Judd SE, Shikany JM, Newby PK. Food intake does not differ between obese women who are metabolically healthy or abnormal. J Nutr. 2014;144:2018–26.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  76. 76.••

    Chooi YC, Ding C, Chan Z, Choo J, Sadananthan SA, Michael N, et al. Moderate weight loss improves body composition and metabolic function in metabolically unhealthy lean subjects. Obesity (Silver Spring). 2018;26:1000–7. A pioneer study that examines the effects of diet-induced weight loss (5%) on body composition, fat distribution, and metabolic function (insulin secretion and sensitivity, lipid profile) in metabolically unhealthy normal weight subjects. Results indicated widespread benefits of weight loss.

    CAS  Article  Google Scholar 

  77. 77.

    Magkos F, Fraterrigo G, Yoshino J, Luecking C, Kirbach K, Kelly SC, et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;23:591–601.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  78. 78.•

    Martinez-Gomez D, Lavie CJ, Hamer M, Cabanas-Sanchez V, Garcia-Esquinas E, Pareja-Galeano H, et al. Physical activity without weight loss reduces the development of cardiovascular disease risk factors - a prospective cohort study of more than one hundred thousand adults. Prog Cardiovasc Dis. 2019;62:522–30. A large prospective study (~6 years) in Asians that demonstrates that an increase in physical activity can reduce risk of developing several metabolic abnormalities (diabetes, metabolic syndrome, hypertension, hypercholesterolemia, dyslipidemia, and inflammation), even in the absence of changes in body weight.

    Article  PubMed  Google Scholar 

  79. 79.

    Murakami K, Livingstone MBE, Sasaki S. Diet quality scores in relation to metabolic risk factors in Japanese adults: a cross-sectional analysis from the 2012 National Health and nutrition survey, Japan. Eur J Nutr. 2019;58:2037–50.

    CAS  Article  PubMed  Google Scholar 

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Klitgaard, H.B., Kilbak, J.H., Nozawa, E.A. et al. Physiological and Lifestyle Traits of Metabolic Dysfunction in the Absence of Obesity. Curr Diab Rep 20, 17 (2020).

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  • Metabolic disease
  • Cardiometabolic risk
  • Body fat distribution
  • Metabolically obese normal weight
  • Metabolically abnormal lean