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Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial
Open accessAbstract
Background: We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. Methods: We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging. Results: Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m 2 ), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (−21.0% versus −11.5% for the MED/LC; P <0.001), and the MED/LC group decreased reported carbohydrates intake (−39.5% versus −21.3% for the low-fat group; P <0.001). The PA + groups significantly increased the metabolic equivalents per week versus the PA − groups (19.0 versus 2.1; P =0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LC PA+ group ( P <0.05). VAT (−22%), intrahepatic (−29%), and intrapericardial (−11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA + with either diet had a significantly greater effect on decreasing VAT (mean of difference, −6.67cm 2 ; 95% confidence interval, −14.8 to −0.45) compared with PA − . The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats ( P <0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin. Conclusions: Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01530724.
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“Interestingly, there is convincing evidence that reduction in visceral adipose tissue in response to exercise can be obtained in the absence of substantial weight loss.”
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BackgroundObesity and cardiovascular disease: beyond body weight and energy balance
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Classification, Diagnosis, and Treatment of Obesity-Related Heart Diseases
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“55,56 Hennein et al. found that longitudinal improvements in diet quality, quantified by increases in measures such as the Mediterranean diet quality score, were associated with reductions in visceral and pericardial fat accumulation during * 6 years of follow-up.”
Goldberg, D. T., Meir, A. Y., Tsaban, G., Rinott, E., Kaplan, A., Zelicha, H., Klöting, N., Ceglarek, U., Iserman, B., Shelef, I., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000000867 · Cited by 8
“We used the CENTRAL trial baseline data [29] as a validation set.”
Self-citationGepner, Y., Goldstein, N., Shelef, I., Schwarzfuchs, D., Zelicha, H., Meir, A. Y., Tsaban, G., & Grossman, E. (2021) · Journal of General Internal Medicine · doi:10.1007/s11606-021-06655-2 · Cited by 9
Self-citationGarcía-Pérez-de-Sevilla, G., Cobo-Vicente, F., Thuissard, I. J., Guido, O. B., & Pérez, M. (2021) · American Journal of Health Promotion · doi:10.1177/08901171211014726 · Cited by 9
Bo, J., & Yang, M. (2025) · BMC Public Health · doi:10.1186/s12889-025-24393-6 · Cited by 6
“Waters et al., in an 18-month randomized controlled trial, reported that aerobic exercise independently contributed to lower VFM [13].”
Kazeminasab, F., Mahboobi, M. H., Mohebinejad, M., Nojoumi, M., Belyani, S., CAMERA, D. M., Moradi, S., & Bagheri, R. (2025) · Current Developments in Nutrition · doi:10.1016/j.cdnut.2025.104574 · Cited by 6
“A total of 1488 participants were included, with sample sizes ranging from 14 [47] to 278 [48].”
InfluentialUs, G. D., Innocenti, F., Koc, Ö. M., Alagoz, A. E., Yumuk, V., Gungor, Z. B., & Koek, G. H. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000856 · Cited by 7
Gál, A. R., Szokodi, I., Vizvári, Z., Győrfi, N., Vereczkei, A. G., Petykó, Z., Karádi, Z., & Tóth, A. (2026) · Antioxidants · doi:10.3390/antiox15060710 · Cited by 6
“These ectopic deposits, together with their lipotoxic metabolites, initiate a cascade of organelle dysfunction and redox imbalance that drives cellular injury and systemic metabolic perturbation [33–35].”
Lechner, K., Kia, S., von Korn, P., Dinges, S. M.-T., Mueller, S., Tjønna, A. E., Wisløff, U., Craenenbroeck, E. M. V., Pieske, B. M., Adams, V., et al. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1329633 · Cited by 5
Banack, H. R., Cook, C. E., Grandi, S. M., Scime, N. V., Andary, R., Follis, S., Allison, M., Manson, J. E., Jung, S. Y., Wild, R. A., et al. (2024) · Human Reproduction · doi:10.1093/humrep/deae118 · Cited by 6
“These results could have broad implications for primary prevention of chronic disease risk in postmenopausal women because visceral fat is a modifiable risk factor via diet, exercise, and medication (Gepner et al. , 2018; Wilding et al. , 2021).”
Soltani, S., Meshkini, F., Torabinasab, K., Razmpoosh, E., Toupchian, O., Zeraattalab-Motlagh, S., Hemmati, A., Sangsefidi, Z. S., & Abdollahi, S. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01721-9 · Cited by 6
“…without other health conditions ( n = 31) [18–23, 25, 27, 29, 30, 32, 36–39, 43, 45–47, 49, 51, 57, 59, 62]; others involved obese individuals with metabolic disorders ( n = 9) [17, 24, 26, 34, 35, 41, 44, 53, 61], or patients with metabolic syndrome or/and diabetes ( n = 4) [31, 42, 52, 54].”
Polyakova, O. A., Ostroumova, O. D., Ковалева, Г. П., & Павлеева, Е. Е. (2021) · Medical alphabet · doi:10.33667/2078-5631-2021-29-13-20 · Cited by 5
Goldenshluger, A., Maor, T., -Kagan, R. V., Romano‐Zelekha, O., & Gepner, Y. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.878202 · Cited by 6
Self-citationXue, Y., Li, J., Xu, Y.-N., Cui, J.-S., Li, Y., Lu, Y.-Q., Luo, X.-Z., Liu, D.-Z., Huang, F., Zeng, Z., et al. (2023) · BMC Public Health · doi:10.1186/s12889-023-16815-0 · Cited by 5
“…trial aiming to evaluate the effects of dietary interventions on the mobilization of fat storage pools found that a Mediterranean low-carbohydrate dietary pattern reduced the BF% and the total amount of visceral adiposity, with this change in lipid traits being independent of a given BMI [55].”
BackgroundZelber‐Sagi, S. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.01.010 · Cited by 6
Gesättigte Fettsäuren und kardiovaskuläres Risiko
Worm, N., Weingärtner, O., Schulze, P. C., & Lechner, K. (2021) · Herz · doi:10.1007/s00059-021-05067-6 · Cited by 5
“Die isolierte Betrachtung des Einflusses einzelner Fettsäuren auf ausgewählte Surrogatparameter kardiovaskulärer Gesundheit wie z.B. das LDL-C ermöglicht keine sinnvolle klinische Einschätzung des Effekts von Lebensmitteln oder Ernährungsmustern auf das globale kardiovaskuläre Risiko und ist daher wohl wenig zielführe…”
InfluentialRøstad‐Tollefsen, H. K., Kolset, S. O., Retterstøl, K., Hesselberg, H., & Nordstrøm, M. (2023) · Food & Nutrition Research · doi:10.29219/fnr.v67.9505 · Cited by 5
Mashayekhi, G., Ashtary‐Larky, D., Karimi, M., Asbaghi, O., Rezaeyeh, A. P., Shouhani, Z., Hosseini, A. Z., & Naderian, M. (2026) · Food Science & Nutrition · doi:10.1002/fsn3.71526 · Cited by 4
“…et al. 2012; Sánchez-Muniz et al. 2012; Burns-Whitmore et al. 2014; Müllner et al. 2014; Njike et al. 2015; Bamberger et al. 2017; Rock et al. 2017; Gepner et al. 2018; Holscher et al. 2018; Fatahi et al. 2019; Sanchis et al. 2019; Tindall et al. 2019; Tuccinardi et al. 2019; Al Abdrabalnabi et…”
Hirose, K., Nakanishi, K., Daimon, M., Iwama, K., Yoshida, Y., Mukai, Y., Yamamoto, Y., Seki, H., Hirokawa, M., Nakao, T., et al. (2024) · JACC Advances · doi:10.1016/j.jacadv.2024.100973 · Cited by 4
Personalisierte Behandlungskonzepte bei arterieller Hypertonie
Lechner, K., & Schunkert, H. (2021) · Herz · doi:10.1007/s00059-020-05010-1 · Cited by 4
Chronic positive mass balance is the actual etiology of obesity: A living review
Manninen, A. H. (2023) · Global Translational Medicine · doi:10.36922/gtm.222 · Cited by 4
Pachter, D., Klein, H., Kamer, O., Toren, D. T. G., Alufer, L., Karamani, N. E., Atlas, T., Yaary, A., Hagbi, I., Chassidim, Y., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-71141-4 · Cited by 7
“The CENTRALtrial,conductedfrom2012to2014,enrolled278participants with abdominal obesity (WC> 102 cm in men, >88 cm in women) and/ or dyslipidemia (triglycerides>150mg/dL, HDL-C 40 mg/dL in men, 50 mg/dL in women), with an 18-month retention rate of 86.3% 9 .”
InfluentialSelf-citationHaynes, P. L., Howe, G. W., Silva, G. E., Quan, S. F., Thomson, C. A., Glickenstein, D. A., Sherrill, D. L., Gengler, D. N., Yingst, A., Mayer, C., et al. (2022) · Obesity · doi:10.1002/oby.23513 · Cited by 3
“ized controlled trials have shown that visceral adipose tissue may be uniquely responsive to engagement in physical activity [3], independent of exercise intensity or changes in body mass [4].”
BackgroundWang, J., Tian, S., Du, J., Du, S., Chen, W., & Liu, Y. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02533-6 · Cited by 3
“While the impact on body mass or total fat reduction is relatively weak, convincing evidence has shown that exercise training has an independent effect on VAT loss [3, 5, 6], which could provide significant health benefits.”
Magkos, F., Ataran, A., Javaheri, A., & Mittendorfer, B. (2023) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000946 · Cited by 3
Paradigmenwechsel in den Empfehlungen zur Ernährung bei Typ-2-Diabetes
Lechner, K., McKenzie, A. L., & Worm, N. (2021) · Info Diabetologie · doi:10.1007/s15034-020-3646-0 · Cited by 3
“Besonders vorteilhaft wirken mediterran ausgerichtete LowCarbDiäten [44].”
BackgroundInfluentialTreatment for Childhood Obesity: Using a Biological Model to Inform Dietary Targets
Ebbeling, C. B., & Ludwig, D. S. (2022) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2022.12.004 · Cited by 3
Liu, H., Duan, J., Guan, G., Rong, P., & Jin, P. (2025) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s564591 · Cited by 2
Tian, S., Han, J., Zhang, Z., Du, J., Chen, W., & Liu, Y. (2025) · European Journal of Applied Physiology · doi:10.1007/s00421-025-06097-2 · Cited by 2
“While surgical, pharmacological and dietary approaches reduce total body fat more effectively, exercise remains indispensable for its safety and comprehensive health ben - efits—with a notable advantage in preferentially reducing visceral adiposity (Gepner et al. 2018 ; Verheggen et al. 2016 ).”
Slettahjell, H. B., Strøm, V., Thoresen, M., Strøm, M., Glott, T., Biering-Sørensen, F., & Henriksen, C. (2026) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2026.103133 · Cited by 2
Klein, H., Alufer, L., Toren, D. T. G., Pachter, D., Kamer, O., Karamani, N. E., Chassidim, Y., Shelef, I., Rudich, A., Yoel, U., et al. (2026) · Circulation · doi:10.1161/circulationaha.125.079009 · Cited by 3
“…previous analyses from the CENTRAL and DIRECT-PLUS trials showed no consistent adverse associations between superficial SAT and metabolic outcomes during the 18-month interventions, 3,4,11 the current findings suggest that a change in superficial SAT is linked to long-term cardiometabolic state.”
Self-citationAhmad, S., Sul, H. H., Danpanichkul, P., de Souza, M. H. G., Petrov, M. S., & The Global Intrapancreatic FaT (GIFT) Alliance (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00737-0 · Cited by 3
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Effects of 1,144 km of road cycling performed in 7 days: a cardiometabolic imaging study
Chartrand, D. J., Murphy-Després, A., Lemieux, I., Larose, É., Poirier, P., Després, J., & Alméras, N. (2024) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00098.2024 · Cited by 2
Metadata
- Authors
- Gepner, Y., Shelef, I., Schwarzfuchs, D., Zelicha, H., Tene, L., Yaskolka Meir, A., Tsaban, G., Cohen, N., Bril, N., Rein, M., Serfaty, D., Kenigsbuch, S., Komy, O., Wolak, A., Chassidim, Y., Golan, R., Avni-Hassid, H., Bilitzky, A., Sarusi, B., Goshen, E., Shemesh, E., Henkin, Y., Stumvoll, M., Blüher, M., Thiery, J., Ceglarek, U., Rudich, A., Stampfer, M. J., & Shai, I.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Soroka Medical Center (IL)
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Y.G., H.Z., L.T., A.Y.M., G.T., N.C., N.B., M.R., D.S., S.K., O.K., R.G., H.A.-H., A.B., E.S., A.R., I.S.).
- Shaare Zedek Medical Center (IL)
- Shimon Peres Negev Nuclear Research Center (IL)
- Department of Medicine, University of Leipzig, Germany (M.S., M.B., J.T., U.C.).
- Leipzig University (DE)
- Brigham and Women's Hospital (US)
- Corresponding author
- Gepner, Yftach
- Shelef, Ilan
- Schwarzfuchs, Dan
- ORCID
- Venue
- Circulation
- Published
- 2018-03-13
- Volume
- 137
- Issue
- 11
- Pages
- 1143-1157
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W3016784104
- Semantic Scholar
- 09fc50175977a3f18864dc55ed917ee21fe2e738
- Cited by
- 279
- References
- 51
- Citations by year
- 2026: 32 · 2025: 27 · 2024: 30 · 2023: 43 · 2022: 47 · 2021: 45 · 2020: 26 · 2019: 18 · 2018: 11
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Circulation (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- Brigham and Women's Hospital
- Harvard T.H. Chan School of Public Health
- Deutsche Forschungsgemeinschaft
- Ben-Gurion University of the Negev
- Topics
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- adipose tissue redistribution, visceral adipose tissue, abdominal obesity, dyslipidemia, Mediterranean diet, low-carbohydrate diet, low-fat diet, Juglans regia, physical activity, intrahepatic fat, intermuscular fat, renal sinus fat, subcutaneous adipose tissue, weight loss, sedentary adults, workplace interventions, magnetic resonance imaging
- MeSH terms
- Healthy Lifestyle, Adipose Tissue, Adult, Aged, Female, Humans, Israel, Lipids, Magnetic Resonance Imaging, Male, Middle Aged, Predictive Value of Tests, Time Factors, Weight Loss, Exercise, Treatment Outcome, Diet, Fat-Restricted, Diet, Mediterranean, Risk Reduction Behavior, Adiposity, Dyslipidemias, Diet, Carbohydrate-Restricted, Obesity, Abdominal
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