The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity
Open accessAbstract
SUMMARY Although 5%–10% weight loss is routinely recommended for people with obesity, the precise effects of 5% and further weight loss on metabolic health are unclear. We conducted a randomized controlled trial that evaluated the effects of 5.1±0.9% (n=19), 10.8±1.3% (n=9) and 16.4±2.1% (n=9) weight loss, and weight maintenance (n=14) on metabolic outcomes. Five percent weight loss improved adipose tissue, liver and muscle insulin sensitivity, and β-cell function, without a concomitant change in systemic or subcutaneous adipose tissue markers of inflammation. Additional weight loss further improved β-cell function and insulin sensitivity in muscle, and caused stepwise changes in adipose tissue mass, intrahepatic triglyceride content, and adipose tissue expression of genes involved in cholesterol flux, lipid synthesis, extracellular matrix remodeling and oxidative stress. These results demonstrate that moderate 5% weight loss improves metabolic function in multiple organs simultaneously, and progressive weight loss causes dose-dependent alterations in key adipose tissue biological pathways.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Weight loss clearly improves insulin sensitivity but the effects in different organ systems have individual variability depending upon the duration and extent of the metabolic dysregulation.”
From Effect of exercise training on insulin-stimulated glucose disposal: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [63]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, reductions in excess abnormal body fat ameliorate the systemic proinflammatory and prothrombotic milieu associated with obesity. 31”
From Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (2023) · cites this paper as [31]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A 10–15% loss may induce remission of T2D or MASLD.”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [71]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In general, insulin-mediated suppression of lipolysis in adipose tissue and suppression of HGP occur maximally at 5% to 8% weight loss 63, 64.”
From Effect of exercise training on insulin-stimulated glucose disposal: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [63]
The cited source says what the claim attributes to it.
In the citing paper
“Insulin-mediated glucose disposal in skeletal muscle continues to increase with additional weight loss 63.”
From Effect of exercise training on insulin-stimulated glucose disposal: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [63]
The cited source says what the claim attributes to it.
In the citing paper
“A weight loss of ≥ 5% represents the first clinically meaningful milestone, associated with improved metabolism, enhanced glucose metabolism and blood pressure.”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [71]
The cited source says what the claim attributes to it.
In the citing paper
“Interestingly, changes in hepatic and adipose tissue insulin sensitivity plateaued after 5 % weight loss, while insulin-mediated skeletal muscle glucose uptake as well as reduction of intrahepatic lipid content continued with progressive weight loss [45].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [45]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“While > 20% is typically required to reverse advanced metabolic or hepatic disease [71].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [71]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041 · cited 2×
“People with obesity and metabolic abnormalities often have concomitant systemic and adipose tissue ‘‘inflammation,’’ manifested by increased circulating inflammatory proteins and white blood cells, and increased subcutaneous adipose tissue macrophages, pro-inflammatory CD4 T-lymphocytes, and increased gene expression…”
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199 · cited 4×
“…inflammation, manifested by alterations in adipose tissue immune cell populations and increased gene expression of pro-inflammatory cytokines and chemokines, which cause systemic inflammation and insulin resistance (Berg and Scherer, 2005; Ferrante, 2007; Hotamisligil, 2006; Sun et al., 2013).”
InfluentialThe metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
Chen, X., Xiu, M., Xing, J., Yu, S., Min, D., & Guo, F. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479439 · Cited by 5,760
Kopelman, P. G. (2000) · Nature · doi:10.1038/35007508 · Cited by 4,795 · cited 2×
“…including insulin resistance, b cell dysfunction, nonalcoholic fatty liver disease, dyslipidemia, and hypertension, which are important risk factors for the development of serious medical complications such as type 2 diabetes and coronary heart disease (Klein et al., 2002; Kopelman, 2000).”
2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults
Jensen, M. D., Ryan, D. H., Apovian, C. M., Ard, J. D., Comuzzie, A. G., Donato, K. A., Hu, F. B., Hubbard, V. S., Jakicic, J. M., Kushner, R. F., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.11.004 · Cited by 4,058
Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L., & Spiegelman, B. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117936 · Cited by 3,543 · cited 2×
“Although a mechanistic relationship between inflammation andmetabolic dysfunction has been demonstrated in rodent models (Berg and Scherer, 2005; Brestoff and Artis, 2015; Ferrante, 2007; Hotamisligil, 2006; Hotamisligil et al., 1995; Sun et al., 2013), the importance of low-grade inflammation in the pathogenesis of o…”
Kim, H. J., Park, S. Y., Choi, Y. J., Han, S. J., Lee, K. W., & Kim, D. J. (2013) · Hormone Research in Paediatrics · doi:10.1159/000348848 · Cited by 3,061
Adipose Tissue, Inflammation, and Cardiovascular Disease
Berg, A. H., & Scherer, P. E. (2005) · Circulation Research · doi:10.1161/01.res.0000163635.62927.34 · Cited by 2,113 · cited 4×
“…inflammation, manifested by alterations in adipose tissue immune cell populations and increased gene expression of pro-inflammatory cytokines and chemokines, which cause systemic inflammation and insulin resistance (Berg and Scherer, 2005; Ferrante, 2007; Hotamisligil, 2006; Sun et al., 2013).”
InfluentialCorrect Homeostasis Model Assessment (HOMA) Evaluation Uses the Computer Program
Lévy, J., Matthews, D. R., & Hermans, M. P. (1998) · Diabetes Care · doi:10.2337/diacare.21.12.2191 · Cited by 2,023 · cited 2×
“Subjects with obesity had evidence of multi-organ insulin resistance (based on a homeostasis model assessment of insulin resistance score >2.0 [Levy et al., 1998] and results of a hyperinsulinemic-euglycemic clamp procedure conducted in conjunction with infusion of stable isotopically labeled…”
Influential
Flagged first, then by citations
Cited by
Sorted by citations
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032183 · Cited by 5,205
“, prediabetes, hypertension, and obstructive sleep apnea).(1,20,21,27) In the semaglutide group, approximately 70% of participants achieved a weight loss of at least 10%, and approximately 50% achieved a weight loss of at least 15%.”
BackgroundMechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
Tirzepatide Once Weekly for the Treatment of Obesity
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206038 · Cited by 3,838
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., Hardt-Lindberg, S., Hovingh, G. K., Kahn, S. E., Kushner, R. F., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2307563 · Cited by 3,236
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947
Mechanisms, Pathophysiology, and Management of Obesity
Heymsfield, S. B., & Wadden, T. A. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1514009 · Cited by 1,867
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
“It has been suggested that pronounced weight loss over time can lead to improvements in adipose tissue inflammation that were not observed in the same subjects following acute moderate weight loss (552).”
BackgroundAdipose tissue dysfunction as determinant of obesity-associated metabolic complications
Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G. A., Beguinot, F., & Miele, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092358 · Cited by 1,575
“Nevertheless, these approaches are difficult to maintain in the long term [8].”
BackgroundCatalano, P. M., & Shankar, K. (2017) · BMJ · doi:10.1136/bmj.j1 · Cited by 1,306
Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes
Zatterale, F., Longo, M., Naderi, J., Raciti, G. A., Desiderio, A., Miele, C., & Beguinot, F. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2019.01607 · Cited by 1,180
“The improved glycemic control after weight loss is due, in part, to the dysregulated expression of genes involved in cholesterol flux, lipid synthesis, ECM remodeling, and oxidative stress (Magkos et al., 2016).”
BackgroundAnti-obesity drug discovery: advances and challenges
Müller, T. D., Blüher, M., Tschöp, M. H., & DiMarchi, R. D. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00337-8 · Cited by 1,021
Why does obesity cause diabetes?
Klein, S., Gastaldelli, A., Yki-Järvinen, H., & Scherer, P. E. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.012 · Cited by 939
“…plasma triglyceride and increased HDL-cholesterol concentrations, decreased fasting blood glucose and insulin concentrations, increased oral glucose tolerance and insulin sensitivity, and decreased risk of type 2 diabetes in people who are lean, overweight, or obese (Manolopoulos et al., 2010).”
BackgroundSelf-citationWeight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over
Ryan, D. H., & Yockey, S. R. (2017) · Current Obesity Reports · doi:10.1007/s13679-017-0262-y · Cited by 831
Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease
Smith, G. I., Shankaran, M., Yoshino, M., Schweitzer, G. G., Chondronikola, M., Beals, J. W., Okunade, A. L., Patterson, B. W., Nyangau, E., Field, T., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci134165 · Cited by 771
“Even 48 h of calorie restriction causes a marked decline in IHTG content (50), and at any given percent weight loss, the relative decrease in IHTG content is much greater than the relative decrease in whole-body or intra-abdominal adipose tissues (51).”
BackgroundSelf-citationThe aetiology and molecular landscape of insulin resistance
James, D. E., Stöckli, J., & Birnbaum, M. J. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00390-6 · Cited by 736
Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence
Kerr, J., Anderson, C. A. M., & Lippman, S. M. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30411-4 · Cited by 706
Metabolically healthy obesity: facts and fantasies
Smith, G. I., Mittendorfer, B., & Klein, S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129186 · Cited by 677
Self-citationGabel, K., Hoddy, K. K., Haggerty, N., Song, J., Kroeger, C. M., Trepanowski, J. F., Panda, S., & Varady, K. A. (2018) · Nutrition and Healthy Aging · doi:10.3233/nha-170036 · Cited by 656
“Accumulating evidence suggests that even small amounts of weight loss can lead to improvements in metabolic health [15].”
BackgroundObesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation
Lingvay, I., Sumithran, P., Cohen, R. V., & le Roux, C. W. (2022) · The Lancet · doi:10.1016/s0140-6736(21)01919-x · Cited by 581
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 566
Lowe, D. A., Wu, N., Rohdin-Bibby, L., Moore, A. H., Kelly, N., Liu, Y. E., Philip, E., Vittinghoff, E., Heymsfield, S. B., Olgin, J. E., et al. (2020) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2020.4153 · Cited by 553
Diet and exercise in the prevention and treatment of type 2 diabetes mellitus
Magkos, F., Hjorth, M. F., & Astrup, A. V. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0381-5 · Cited by 507
Self-citationPreserving Healthy Muscle during Weight Loss
Cava, E., Yeat, N. C., & Mittendorfer, B. (2017) · Advances in Nutrition · doi:10.3945/an.116.014506 · Cited by 452
Obesity and the risk of cardiometabolic diseases
Valenzuela, P. L., Carrera-Bastos, P., Castillo-García, A., Lieberman, D. E., Santos-Lozano, A., & Lucia, A. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00847-5 · Cited by 452
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
Yoshino, M., Yoshino, J., Kayser, B. D., Patti, G. J., Franczyk, M. P., Mills, K. F., Sindelar, M., Pietka, T., Patterson, B. W., Imai, S.-I., et al. (2021) · Science · doi:10.1126/science.abe9985 · Cited by 439
“with obesity that we previously studied(19, 34), we estimated that 11 participants per group would be”
BackgroundSelf-citationObesity as a multisystem disease: Trends in obesity rates and obesity‐related complications
Sarma, S., Sockalingam, S., & Dash, S. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14290 · Cited by 485
“However, skeletal muscle insulin resistance persists.(79) Significantly greater weight loss of >15% improves skeletal muscle insulin sensitivity(79) .”
BackgroundAn Integrated View of Immunometabolism
Lee, Y. S., Wollam, J., & Olefsky, J. M. (2018) · Cell · doi:10.1016/j.cell.2017.12.025 · Cited by 452
“have shown that obese subjects who lose 5% of body weight exhibit marked increases in insulin sensitivity despite the fact that they remained obese—just less so (Magkos et al., 2016).”
BackgroundMethodInfluentialGut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention
Liu, Y., Wang, Y., Ni, Y., Cheung, C. K. Y., Lam, K. S. L., Wang, Y., Xia, Z., Ye, D., Guo, J., Tse, M. A., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.001 · Cited by 405
The role of macrophages in obesity-associated islet inflammation and β-cell abnormalities
Ying, W., Fu, W., Lee, Y. S., & Olefsky, J. M. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0286-3 · Cited by 410
Adiponectin, Leptin and Cardiovascular Disorders
Zhao, S., Kusminski, C. M., & Scherer, P. E. (2021) · Circulation Research · doi:10.1161/circresaha.120.314458 · Cited by 415
Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus
Burhans, M. S., Hagman, D. K., Kuzma, J. N., Schmidt, K. A., & Kratz, M. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170040 · Cited by 461
Progress and challenges in anti-obesity pharmacotherapy
Bessesen, D. H., & Van Gaal, L. F. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30236-x · Cited by 347
Karczewski, J., Śledzińska, E., Baturo, A., Jończyk, I., Maleszko, A., Maleszko, A., Samborski, P., Krasińska, B., & Dobrowolska, A. (2018) · European Cytokine Network · doi:10.1684/ecn.2018.0415 · Cited by 321
“Additional weight loss (11-16%) is associated with a reduction in systemic and adipose inflammation and leads to further improvements in -cell function and insulin sensitivity in muscles, reduction in adipose tissue and liver triglycerides, and changes in the expression of genes in adipose tissue involved in cholester…”
BackgroundMetabolically 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 314
Ard, J., Fitch, A., Fruh, S., & Herman, L. (2021) · Advances in Therapy · doi:10.1007/s12325-021-01710-0 · Cited by 297
“Even a modest weight loss of 5% has been shown to improve cardiometabolic risk factors, including reduced systolic blood pressure and plasma triglyceride concentration, and increased multi-organ insulin sensitivity and b-cell function [6].”
BackgroundDeterminants of weight loss maintenance: a systematic review
Varkevisser, R. D. M., van Stralen, M. M., Kroeze, W., Ket, J. C. F., & Steenhuis, I. H. M. (2019) · Obesity Reviews · doi:10.1111/obr.12772 · Cited by 295
“Studies were further conducted in Germany (4) (61–64), Finland (4) (65–68), Japan (3) (69–71), Australia (2) (72,73), Portugal (1) (74,75), Switzerland (76), Denmark (77), Israel (78), France (79), Canada (80) and the Netherlands (81).”
BackgroundSchwarz, J., Noworolski, S. M., Erkin‐Cakmak, A., Korn, N. J., Wen, M., Tai, V., Jones, G. M., Palii, S. P., Velasco-Alin, M., Pan, K. D. H., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.05.043 · Cited by 275
Self-citationStokes, T., Hector, A., Morton, R., McGlory, C., & Phillips, S. (2018) · Nutrients · doi:10.3390/nu10020180 · Cited by 263
“In overweight and obese individuals, the ensuing body mass loss that follows a protracted energy deficit generally confers physical as well as metabolic health benefits such as improved hepatic and skeletal muscle insulin sensitivity, as well as improvements in beta-cell function [78].”
BackgroundThe β3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans
Finlin, B. S., Memetimin, H., Zhu, B., Confides, A. L., Vekaria, H. J., Khouli, R. H. E., Johnson, Z., Westgate, P. M., Chen, J., Morris, A. J., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci134892 · Cited by 261
“Resistin was initially discovered weight loss of more than 16% (46).”
BackgroundObesity: 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 264
“However, even short-term small amounts of weight-loss can show substantial metabolic benefits.(137)”
BackgroundZomer, E., Gurusamy, K., Leach, R., Trimmer, C., Lobstein, T., Morris, S., James, W. P. T., & Finer, N. (2016) · Obesity Reviews · doi:10.1111/obr.12433 · Cited by 236
“Our findings are supported by a recent mechanistic study that demonstrates that moderate 5% weight loss improves metabolic function in multiple organs simultaneously and progressive weight loss causes dose-dependent alterations in key adipose tissue biological pathways (36).”
ResultEffects of diet versus gastric bypass on metabolic function in diabetes
Yoshino, M., Kayser, B. D., Yoshino, J., Stein, R. I., Reeds, D., Eagon, J. C., Eckhouse, S. R., Watrous, J. D., Jain, M., Knight, R., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2003697 · Cited by 246
Self-citationAmerican Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., Ekhlaspour, L., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s008 · Cited by 236
Sargeant, J. A., Henson, J., King, J. A., Yates, T., Khunti, K., & Davies, M. J. (2019) · Endocrinology and Metabolism · doi:10.3803/enm.2019.34.3.247 · Cited by 231
Body composition and cardiometabolic health across the menopause transition
Marlatt, K. L., Pitynski, D., Gavin, K. M., Moreau, K. L., Melanson, E. L., Santoro, N. F., & Kohrt, W. M. (2021) · Obesity · doi:10.1002/oby.23289 · Cited by 261
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
Creanga, A. A., Catalano, P. M., & Bateman, B. T. (2022) · New England Journal of Medicine · doi:10.1056/nejmra1801040 · Cited by 230
Stein, N., & Brooks, K. (2017) · JMIR Diabetes · doi:10.2196/diabetes.8590 · Cited by 191
“Losing as little as 5% of excess body weight improves insulin sensitivity [56].”
BackgroundGomez-Arbelaez, D., Bellido, D., Castro, A. I., Ordoñez-Mayan, L., Carreira, J., Galban, C., Martinez-Olmos, M. A., Crujeiras, A. B., Sajoux, I., & Casanueva, F. F. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2385 · Cited by 214
“The accurate measurement of body composition changes is relevant to assess the contribution of the diet intervention, not only on total body weight but in the changes produced in FM, FFM, VF, and total body water (25, 27).”
BackgroundAmerican Diabetes Association Professional Practice Committee, ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Ekhlaspour, L., Hilliard, M. E., Johnson, E. L., Khunti, K., et al. (2024) · Diabetes Care · doi:10.2337/dc24-s008 · Cited by 213
Cusi, K., Bril, F., Barb, D., Polidori, D., Sha, S., Ghosh, A., Farrell, K., Sunny, N. E., Kalavalapalli, S., Pettus, J., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13584 · Cited by 204
Ryan, B. J., Schleh, M. W., Ahn, C., Ludzki, A. C., Gillen, J. B., Varshney, P., Pelt, D. W. V., Pitchford, L. M., Chenevert, T. L., Gioscia‐Ryan, R. A., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa345 · Cited by 228
Immunologic and endocrine functions of adipose tissue: implications for kidney disease
Zhu, Q., & Scherer, P. E. (2018) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.157 · Cited by 200
Anti-obesity therapy: from rainbow pills to polyagonists
Müller, T. D., Clemmensen, C., Finan, B., DiMarchi, R. D., & Tschöp, M. H. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014803 · Cited by 199
“The decrease in hepatic and intra-abdominal fat accumulation, the improvement of b -cell function, as well as enhanced insulin sensitivity in the liver, adipose tissue, and skeletal muscle, are observed with this degree of weight loss (Magkos et al., 2016; Heymsfield and Wadden, 2017).”
BackgroundAcute dietary fat intake initiates alterations in energy metabolism and insulin resistance
Hernández, E. Á., KAHL, S., Seelig, A., Begovatz, P., Irmler, M., Kupriyanova, Y., Nowotny, B., Nowotny, P., Herder, C., Barosa, C., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89444 · Cited by 205
“Santos SH, et al. Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet.”
BackgroundIs Weight Loss–Induced Muscle Mass Loss Clinically Relevant?
Conte, C., Hall, K. D., & Klein, S. (2024) · JAMA · doi:10.1001/jama.2024.6586 · Cited by 191
Self-citationMetaflammation in obesity and its therapeutic targeting
Schleh, M. W., Caslin, H. L., Garcia, J. N., Mashayekhi, M., Srivastava, G., Bradley, A. B., & Hasty, A. H. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adf9382 · Cited by 197
“%) sufficiently reduced both systemic and AT inflammation ( 99 ).”
BackgroundDiet and exercise in NAFLD/NASH: Beyond the obvious
Semmler, G., Datz, C., Reiberger, T., & Trauner, M. (2021) · Liver International · doi:10.1111/liv.15024 · Cited by 187
Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH)
Do, A., Zahrawi, F. M., & Mehal, W. Z. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01084-2 · Cited by 206
“Moderate weight loss of 5 to 7% improves insulin sensitivity in both adipose and liver tissue 33 , and the intracellular signalling pathways that contribute to insulin resistance in adipose tissue might also contribute to inflammation and steatohepatitis, so these pathways are attractive…”
GLP-1/glucagon receptor co-agonism for treatment of obesity
Sánchez-Garrido, M. A., Brandt, S. J., Clemmensen, C., Müller, T. D., DiMarchi, R. D., & Tschöp, M. H. (2017) · Diabetologia · doi:10.1007/s00125-017-4354-8 · Cited by 175
“When sustained, this degree of weight loss can provide meaningful improvements in metabolism and lipid management [11].”
BackgroundAdipose tissue lipolysis and remodeling during the transition period of dairy cows
Contreras, G. A., Strieder‐Barboza, C., & Raphael, W. (2017) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-017-0174-4 · Cited by 187
“In humans and rodents, the rate of basal lipolysis is determined by adipocyte size and TAG content [10, 15].”
BackgroundObesity in South and Southeast Asia—A new consensus on care and management
Tham, K. W., Abdul Ghani, R., Cua, S. C., Deerochanawong, C., Fojas, M., Hocking, S., Lee, J., Nam, T. Q., Pathan, F., Saboo, B., et al. (2023) · Obesity Reviews · doi:10.1111/obr.13520 · Cited by 187
Linge, J., Birkenfeld, A. L., & Neeland, I. J. (2024) · Circulation · doi:10.1161/circulationaha.124.067676 · Cited by 180
Ghrelin regulation of glucose metabolism
Poher, A.-L., Tschöp, M. H., & Müller, T. D. (2018) · Peptides · doi:10.1016/j.peptides.2017.12.015 · Cited by 186
SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection
Ανδρουτσάκος, Θ., Ansari, N. N., Bakasis, A., Kyrou, I., EFSTATHOPOULOS, E. P., Randeva, H. S., & Kassi, E. N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063107 · Cited by 176
Ding, C., Chan, Z., & Magkos, F. (2016) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000317 · Cited by 160
Self-citationObesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease?
Huttasch, M., Roden, M., & Kahl, S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155937 · Cited by 169
Macrophage Proliferation Sustains Adipose Tissue Inflammation in Formerly Obese Mice
Zamarron, B. F., Mergian, T. A., Cho, K. W., Martinez-Santibañez, G., Luan, D., Singer, K., DelProposto, J. L., Geletka, L. M., Muir, L. A., & Lumeng, C. N.-K. (2016) · Diabetes · doi:10.2337/db16-0500 · Cited by 159
“Inflammation-related gene expression in subcutaneous AT of formerly obese human subjects remains high compared with expression in lean individuals (17,18).”
BackgroundNew insights into the treatment of obesity
Blüher, M., Aras, M., Aronne, L. J., Batterham, R. L., Giorgino, F., Ji, L., Pietiläinen, K. H., Schnell, O., Tonchevska, E., & Wilding, J. P. H. (2023) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15077 · Cited by 158
“These benefits increase with progressively greater weight reduction.(89) With a mean weight TABLE 3 STEP clinical trial programme with efficacy results”
BackgroundCarneiro‐Barrera, A., Amaro‐Gahete, F. J., Guillén‐Riquelme, A., Jurado‐Fasoli, L., Sáez-Roca, G., Martín-Carrasco, C., Buela‐Casal, G., & Ruiz, J. R. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.8212 · Cited by 158
Metabolic Regulation of Adipose Tissue Macrophage Function in Obesity and Diabetes
Appari, M., Channon, K. M., & McNeill, E. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7060 · Cited by 154
“Indeed, intervention studies suggest that even a modest (5%) weight loss, achieved by low-calorie diet, substantially improves metabolic functions in AT, liver and muscle insulin sensitivity, and pancreatic b-cell function (61), suggesting that changes in AT biology and metabolism are critical regulators of disease pa…”
BackgroundWatanabe, 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 157
Locatelli, J. C., Costa, J. G., Haynes, A., Naylor, L. H., Fegan, P. G., Yeap, B. B., & Green, D. J. (2024) · Diabetes Care · doi:10.2337/dci23-0100 · Cited by 152
Moiz, A., Filion, K. B., Toutounchi, H., Tsoukas, M. A., Yu, O. H. Y., Peters, T. M., & Eisenberg, M. J. (2025) · Annals of Internal Medicine · doi:10.7326/annals-24-01590 · Cited by 149
Metabolically healthy obesity: what–s in a name?
Magkos, F. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz133 · Cited by 148
Self-citationAre Lifestyle Therapies Effective for NAFLD Treatment?
El-Agroudy, N. N., Kurzbach, A., Rodionov, R. N., O’Sullivan, J., Roden, M., Birkenfeld, A. L., & Pesta, D. H. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.07.013 · Cited by 144
“and 15–20% protein) gradually reduces IHL in obese, insulin-resistant humans [9,10].”
Drapkina, O. M., Васильевна, К. А., Калинина, А. М., Avdeev, S. M., Викторович, А. М., Alexandrova, L. M., Анциферова, А. А., Dm, A., Ахмеджанов, Н. М., Balanova, Y. А., et al. (2022) · CARDIOVASCULAR THERAPY AND PREVENTION · doi:10.15829/1728-8800-2022-3235 · Cited by 197
Benotti, P. N., Wood, G. C., Carey, D. J., Mehra, V. C., Mirshahi, T., Lent, M. R., Petrick, A. T., Still, C. D., Gerhard, G. S., & Hirsch, A. G. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.005126 · Cited by 137
“Weight loss achieved by any method will improve cardiovascular risk and reverse the abovementioned pathophysiologic sequence.(6) The shortcomings of diet and other lifestyle From the Geisinger Obesity Institute (P.”
MethodWeight loss is a critical factor to reduce inflammation
Bianchi, V. E. (2018) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2018.08.007 · Cited by 142
Obesity and chronic kidney disease: A current review
Nawaz, S., Chinnadurai, R., Al‐Chalabi, S., Evans, P., Kalra, P. A., Syed, A. A., & Sinha, S. (2022) · Obesity Science & Practice · doi:10.1002/osp4.629 · Cited by 147
“management fosters good health outcomes in patients with obesity and reduces mortality,(132) improves glycemic status and triglyceride levels, and better cardiometabolic outcomes are highlighted in the literature.(123,133) In consideration of renal health, targeted weight loss interventions improve outcomes such as mi…”
BackgroundBray, G. A., & Ryan, D. H. (2021) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14200 · Cited by 148
“The loss of fat in critical depots was disproportionately greater than weight loss.(14) The mes-”
BackgroundInfluentialKillion, E. A., Reeves, A. R., ElAzzouny, M. A., Yan, Q.-W., Surujon, D., Griffin, J. D., Bowman, T. A., Wang, C., Matthan, N. R., Klett, E. L., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.01.012 · Cited by 136
Sattler, K. M., Deane, F. P., Tapsell, L., & Kelly, P. J. (2018) · Health Psychology Open · doi:10.1177/2055102918759691 · Cited by 150
“However, just a 5 per cent reduction in body weight in individuals with obesity can result in significant improvements in risk factors associated with these medical conditions (Magkos et al., 2016).”
Intermittent Fasting and Metabolic Health: From Religious Fast to Time‐Restricted Feeding
Hoddy, K. K., Marlatt, K. L., Çetinkaya, H., & Ravussin, É. (2020) · Obesity · doi:10.1002/oby.22829 · Cited by 140
“Even CR-induced weight loss of ~5 to 10% has definitive cardiometabolic health benefits (39).”
BackgroundINTERDISCIPLINARY CLINICAL PRACTICE GUIDELINES "MANAGEMENT OF OBESITY AND ITS COMORBIDITIES"
Dedov, I. I., Shestakova, M. V., Mel'nichenko, G. A., Mazurina, N. V., Andreeva, E. N., Bondarenko, I. Z., Руслановна, Г. З., Dzgoeva, F. K., Елисеев, М. С., Ershova, E. V., et al. (2021) · Obesity and metabolism · doi:10.14341/omet12714 · Cited by 163
Ronald, C. W., Schmidt, M. I., Tam, W. H., McIntyre, D. H., & Catalano, P. M. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)30278-9 · Cited by 136
Benefits of weight loss of 10% or more in patients with overweight or obesity: A review
Tahrani, A. A., & Morton, J. (2022) · Obesity · doi:10.1002/oby.23371 · Cited by 125
Thomas, C. E., Mauer, E. A., Shukla, A. P., Rathi, S., & Aronne, L. J. (2016) · Obesity · doi:10.1002/oby.21533 · Cited by 124
“Achieving 5% to 10% weight loss improves insulin sensitivity and b-cell function (33) and is associated with an increased likelihood of achieving a 20.”
BackgroundKabahizi, A., Wallace, B., Lieu, L., Chau, D., Dong, Y., Hwang, E., & Williams, K. W. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15682 · Cited by 126
“improvements in blood sugar control, BP regulation and triglyceride levels (Magkos et al., 2016; Yanovski & Yanovski, 2014).”
BackgroundTargher, G., Mantovani, A., & Byrne, C. D. (2023) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(22)00338-7 · Cited by 121
Antoni, R., Johnston, K. L., Collins, A. L., & Robertson, M. D. (2018) · British Journal Of Nutrition · doi:10.1017/s0007114517003890 · Cited by 124
“Glucose and lipid homoeostasis can be improved through weight loss((2))”
BackgroundAdipose Tissue Dysfunction in Polycystic Ovary Syndrome
Bril, F., Ezeh, U., Amiri, M., Hatoum, S., Pace, L., Chen, Y.-H., Bertrand, F., Gower, B., & Azziz, R. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad356 · Cited by 123
Tan, H. C., Dampil, O. A., & Marquez, M. M. (2022) · Journal of the ASEAN Federation of Endocrine Societies · doi:10.15605/jafes.037.02.14 · Cited by 135
Is regular exercise an effective strategy for weight loss maintenance?
Foright, R. M., Presby, D. M., Sherk, V. D., Kahn, D., Checkley, L. A., Giles, E. D., Bergouignan, A., Higgins, J. A., Jackman, M. R., Hill, J. O., et al. (2018) · Physiology & Behavior · doi:10.1016/j.physbeh.2018.01.025 · Cited by 113
Aras, M., Tchang, B. G., & Pape, J. (2021) · Nursing Clinics of North America · doi:10.1016/j.cnur.2021.07.008 · Cited by 122
Barrett, S., Begg, S. J., O’Halloran, P., & Kingsley, M. (2018) · BMC Public Health · doi:10.1186/s12889-018-6062-9 · Cited by 118
The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis
Shen, H., Huang, X., Zhao, Y., Wu, D., Xue, K., Yao, J., Wang, Y., Tang, N., & Qiu, Y. (2022) · Nature Communications · doi:10.1038/s41467-022-33800-0 · Cited by 118
Forcano, L., Mata, F., de la Torre, R., & Verdejo‐García, A. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.02.003 · Cited by 103
Effect of Bariatric Surgery on Metabolic Diseases and Underlying Mechanisms
Ji, Y., Lee, H., Kaura, S., Yip, J., Sun, H., Guan, L., Han, W., & Ding, Y. (2021) · Biomolecules · doi:10.3390/biom11111582 · Cited by 108
“A recent study [24] assessed how different levels of weight loss impacted metabolic function and adipose tissue biology.”
Background
Metadata
- Authors
- Magkos, F., Fraterrigo, G., Yoshino, J., Luecking, C., Kirbach, K., Kelly, S. C., de las Fuentes, L., He, S., Okunade, A. L., Patterson, B. W., & Klein, S.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Washington University in St. Louis (US)
- Corresponding author
- Klein, Samuel
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 23
- Issue
- 4
- Pages
- 591-601
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4833627
- OpenAlex
- W2283809486
- Semantic Scholar
- 22c2c95f3eae678f67267c186f68d979ed5b03d6
- Cited by
- 886
- References
- 47
- Citations by year
- 2026: 83 · 2025: 92 · 2024: 95 · 2023: 90 · 2022: 108 · 2021: 97 · 2020: 93 · 2019: 79 · 2018: 64 · 2017: 57 · 2016: 26
- FWCI
- 70.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Longer Life Foundation
- Pershing Square Foundation
- National Institutes of Health (5p60dk020579-35, KL2TR000450, UL1TR000448)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK37948, DK20579, DK56341, R01DK104995, R01DK037948, DK104995, P60-DK-020579, P30DK092950, P30DK056341, P30DK020579)
- National Center for Research Resources (RR-024992, UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- obesity, weight loss, weight maintenance, insulin sensitivity, beta-cell function, adipose tissue, liver, skeletal muscle, intrahepatic triglyceride, adipose tissue inflammation, cholesterol flux, lipogenesis, extracellular matrix remodeling, oxidative stress, dose-dependent effects
- MeSH terms
- Adipose Tissue, Adult, Female, Humans, Insulin, Insulin Resistance, Liver, Male, Middle Aged, Muscles, Obesity, Weight Loss, Insulin-Secreting Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
