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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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Self-citationOne size does not fit all; practical, personal tailoring of the diet to NAFLD patients
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Self-citationMeir, A. Y., Keller, M., Bernhart, S. H., Rinott, E., Tsaban, G., Zelicha, H., Kaplan, A., Schwarzfuchs, D., Shelef, I., Gepner, Y., et al. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01038-0 · Cited by 49
“Randomization and intervention As previously described [25], participants were randomly assigned in two phases: first, two equally hypocaloric diets: a LF diet or a MED/LC diet.”
BackgroundMethodInfluentialSelf-citationCosentino, F., Verma, S., Ambery, P., Treppendahl, M. B., van Eickels, M., Anker, S. D., Cecchini, M., Fioretto, P., Groop, P., Hess, D. A., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad445 · Cited by 66
Impact of Dietary Fiber on Inflammation in Humans
Kabisch, S., Hajir, J., Sukhobaevskaia, V., Weickert, M. O., & Pfeiffer, A. F. H. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052000 · Cited by 54
“Clinical evidence for benefits is mostly seen in studies conducted in Mediterranean countries [73], possibly showing a limited acceptance in other regions (such as Germany, Australia, or the UK) [80–82].”
Pepe, R. B., Lottenberg, A. M., Fujiwara, C. T. H., Beyruti, M., Cintra, D. E., Machado, R. M., Rodrigues, A., Jensen, N. S. O., Caldas, A. P. S., Fernandes, A. E., et al. (2023) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-023-01037-6 · Cited by 59
Fatty infiltration of the pancreas: a systematic concept analysis
Mahyoub, M. A., Elhoumed, M., Maqul, A. H., Almezgagi, M., Abbas, M. A., Jiao, Y., Wang, J., Alnaggar, M., Zhao, P., & He, S. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1227188 · Cited by 43
“A trial comparing Mediterranean (rich in unsaturated fats) and low-fat diets among individuals with abdominal obesity or dyslipidemia, including T2DM cases, reported significantly lower FIP prevalence with the Mediterranean diet (42).”
BackgroundRoss, R., Soni, S., & Houle, S. (2020) · Nutrients · doi:10.3390/nu12040891 · Cited by 52
“Additionally, in response to an 18-month diet and exercise-based intervention among 278 sedentary adults with abdominal obesity, Gepner and colleagues reported that diet combined with exercise results in greater reductions in VAT than diet alone, assessed using MRI [11].”
BackgroundMethodInfluentialSong, Y., Tan, Y., Deng, M., Shan, W., Zheng, W., Zhang, B., Cui, J., Feng, L., Shi, L., Zhang, M., et al. (2023) · MedComm · doi:10.1002/mco2.413 · Cited by 48
“155,156 All the studies reported a significant reduction in EAT volume or pericardial adipose tissue volume.”
BackgroundThe Effect of Mediterranean Diet on Cognitive Functions in the Elderly Population
Klímová, B., Novotný, M., Schlegel, P., & Vališ, M. (2021) · Nutrients · doi:10.3390/nu13062067 · Cited by 43
“[50] combined the MedDiet and a low-carb diet, which reduced carbohydrate intake (initially < 40 g/day, then <70 g/day) and increased protein and fat intake.”
BackgroundAkbulut, U. E., Işık, İ. A., Atalay, A., Eraslan, A., Durmus, E., Turkmen, S., & Yurttas, A. S. (2021) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637486.2021.1979478 · Cited by 43
European ‘NAFLD Preparedness Index’ — Is Europe ready to meet the challenge of fatty liver disease?
Lazarus, J. V., Palayew, A., Carrieri, P., Ekstedt, M., Marchesini, G., Novak, K., Ratziu, V., Romero‐Gómez, M., Tacke, F., Zelber‐Sagi, S., et al. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100234 · Cited by 45
Eating, diet, and nutrition for the treatment of non-alcoholic fatty liver disease
Semmler, G., Datz, C., & Trauner, M. (2022) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0364 · Cited by 43
“Interestingly, this effect was achieved despite only moderate weight loss, again supporting favorable effects of MD beyond calorie restriction.(80) Recently, the “DIRECT PLUS” RCT demonstrated a successful (and durable) weight loss and decrease in IHLC following a hypocaloric MD after 18 months.”
ResultMa, W., Wu, W., Wen, W., Xu, F., Han, D., Lyu, J., & Huang, Y. (2022) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223221122478 · Cited by 39
Epigenetics in Precision Nutrition
Li, X., & Qi, L. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12040533 · Cited by 40
“conducted a study in the CENTRAL MRI randomized controlled trial, an 18-month lifestyle intervention of either low fat or Mediterranean/low carbohydrate diets [97,98].”
MethodTarsitano, M. G., Pandozzi, C., Muscogiuri, G., Sironi, S., Pujia, A., Lenzi, A., & Giannetta, E. (2022) · Nutrients · doi:10.3390/nu14142926 · Cited by 30
“Although the specific mechanisms of action have not yet been well identified, anti-inflammatory therapy, statins and lifestyle alone could change positively the EAT characterization [45,55,57].”
BackgroundHadefi, A., Arvanitakis, M., Trépo, E., & Zelber‐Sagi, S. (2023) · United European Gastroenterology Journal · doi:10.1002/ueg2.12443 · Cited by 40
Melián-Fleitas, L., Franco-Pérez, Á. M., Caballero, P., Sanz-Lorente, M., Wanden-Berghe, C., & Sanz‐Valero, J. (2021) · Nutrients · doi:10.3390/nu13113945 · Cited by 35
“The main pathologies observed in the study population were overweight and obesity [22–25,35,36,38,40–43,46,50,52]; overweight [26,29,53,55]; obesity [37,45,51]; overweight, obesity and diabetes [31,32,34,39,47,48]; abdominal obesity and dyslipidemia [27,30]; overweight and musculoskeletal disorders [28]; obesity, diab…”
BackgroundResultInfluentialPractical Lifestyle Management of Nonalcoholic Fatty Liver Disease for Busy Clinicians
Zelber‐Sagi, S., & Moore, J. B. (2024) · Diabetes Spectrum · doi:10.2337/dsi23-0009 · Cited by 39
“The fi rst showed the superiority of a Mediterranean diet that was also low in carbohydrate over a low-fat diet in decreasing intrahepatic fat (30).”
BackgroundGiovannucci, E. L. (2018) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djy091 · Cited by 35
Hebbar, P., Nizam, R., Melhem, M., Alkayal, F., Elkum, N. B., John, S. E., Tuomilehto, J., Alsmadi, O. A., & Thanaraj, T. A. (2018) · Journal of Lipid Research · doi:10.1194/jlr.p080218 · Cited by 34
“Factors that contribute to abnormal blood lipid levels include lipid mobilization and metabolism (8),”
BackgroundBMI but not central obesity predisposes to airway closure during bronchoconstriction
Peters, U., Subramanian, M., Chapman, D. G., Kaminsky, D. A., Irvin, C. G., Wise, R. A., Skloot, G. S., Bates, J. H. T., & Dixon, A. E. (2019) · Respirology · doi:10.1111/resp.13478 · Cited by 32
Limbachia, J., Ajmeri, M. S., Keating, B. J., de Souza, R. J., & Anand, S. S. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-059666 · Cited by 32
The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols
Meir, A. Y., Tuohy, K. M., von Bergen�, M., Krajmalnik‐Brown, R., Heinig, U., Zelicha, H., Tsaban, G., Rinott, E., Kaplan, A., Aharoni, A., et al. (2021) · Nutrients · doi:10.3390/nu13061866 · Cited by 31
“Participants were instructed to adopt a calorie-restricted Mediterranean diet as described in our previous trials: DIRECT [31] and CENTRAL [32] trials, supplemented with 28 g/day of walnuts (containing 440 mg polyphenols/day; gallic acid equivalents (GAE) [33]).”
MethodSelf-citationAuthors, & Collaborators: (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1880-2388 · Cited by 30
Dobbie, L. J., Burgess, J., Hamid, A., Nevitt, S. J., Hydes, T., Alam, U., & Cuthbertson, D. J. (2024) · Nutrients · doi:10.3390/nu16071030 · Cited by 34
Arsenault, B. J., Carpentier, A. C., Poirier, P., & Després, J. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.117546 · Cited by 34
Lifestyle factors and visceral adipose tissue: Results from the PREDIMED-PLUS study
Galmes-Panades, A. M., Konieczna, J., Abete, I., Colom, A., Rosique-Esteban, N., Zulet, M. Á., Ruiz, Z. V., Estruch, R., Vidal, J., Toledo, E., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210726 · Cited by 29
Nutrition in Gastrointestinal Disease: Liver, Pancreatic, and Inflammatory Bowel Disease
Storck, L. J., Imoberdorf, R., & Ballmer, P. E. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8081098 · Cited by 28
“A Mediterranean diet low in carbohydrates mobilizes more liver fat compared to a low fat diet with a similar weight loss [17].”
BackgroundZhang, F., Dang, M., Zhang, W., Wang, Y., Kord‐Varkaneh, H., Nazary-Vannani, A., Santos, H. O., Tan, S. C., Clark, C. C. T., Zanghelini, F., et al. (2020) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2020.102395 · Cited by 30
Yu, F., Fan, Y., Sun, H., Li, T., Dong, Y., & Pan, S. (2022) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2022.109881 · Cited by 28
Epicardial Adipose Tissue in Myocardial Disease: From Physiology to Heart Failure Phenotypes
Antonopoulos, A. S., Papastamos, C., Cokkinos, D. V., Tsioufis, K. P., & Tousoulis, D. (2023) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2023.101841 · Cited by 29
Jabbour, J., Rahme, M., Mahfoud, Z. R., & Fuleihan, G. E. (2022) · Endocrine · doi:10.1007/s12020-021-02951-3 · Cited by 29
“Indeed, another study revealed a 22% reduction in VAT area with lifestyle interventions (Mediterranean diet & physical activity) compared to a low fat diet without an exercise component [43].”
BackgroundKim, J. E., Baek, Y., Jeong, K., & Lee, S. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.910481 · Cited by 28
Diedisheim, M., Poitou, C., Genser, L., Amouyal, C., Bouillot, J., Ciangura, C., Oppert, J., Clément, K., & Aron‐Wisnewsky, J. (2020) · Obesity Surgery · doi:10.1007/s11695-020-05075-1 · Cited by 26
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Self-citationLevakov, G., Kaplan, A., Meir, A. Y., Rinott, E., Tsaban, G., Zelicha, H., Blüher, M., Ceglarek, U., Stümvoll, M., Shelef, I., et al. (2023) · eLife · doi:10.7554/elife.83604 · Cited by 27
Self-citationNankam, P. A. N., Blüher, M., Kehr, S., Klöting, N., Krohn, K., Adams, K., Stadler, P. F., Mendham, A. E., & Goedecke, J. H. (2020) · Scientific Reports · doi:10.1038/s41598-020-66868-z · Cited by 25
Self-citationGagnon, É., Pelletier, W., Gobeil, É., Bourgault, J., Manikpurage, H. D., Maltais‐Payette, I., Abner, E., Taba, N., Esko, T., Mitchell, P. L., et al. (2022) · Communications Medicine · doi:10.1038/s43856-022-00196-3 · Cited by 25
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Self-citationDietary Treatment for NAFLD: New Clinical and Epidemiological Evidence and Updated Recommendations
Zelber‐Sagi, S. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1729971 · Cited by 23
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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