{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:47:19Z","timestamp":1762674439056,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK074932; DK112657"],"award-info":[{"award-number":["DK074932; DK112657"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["CNPq 310030\/2015-3; 312675\/2018-6"],"award-info":[{"award-number":["CNPq 310030\/2015-3; 312675\/2018-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Overfeeding of a hypercaloric diet leads to obesity, diabetes, chronic inflammation, and fatty liver disease. Although limiting fat or carbohydrate intake is the cornerstone for obesity management, whether lowering fat or reducing carbohydrate intake is more effective for health management remains controversial. This study used murine models to determine how dietary fat and carbohydrates may influence metabolic disease manifestation. Age-matched C57BL\/6J mice were fed 2 hypercaloric diets with similar caloric content, one with very high fat and low carbohydrate content (VHF) and the other with moderately high fat levels with high sucrose content (HFHS) for 12 weeks. Both groups gained more weight and displayed hypercholesterolemia, hyperglycemia, hyperinsulinemia, and liver steatosis compared to mice fed a normal low-fat (LF) diet. Interestingly, the VHF-fed mice showed a more robust adipose tissue inflammation compared to HFHS-fed mice, whereas HFHS-fed mice showed liver fibrosis and inflammation that was not observed in VHF-fed mice. Taken together, these results indicate macronutrient-specific tissue inflammation with excess dietary fat provoking adipose tissue inflammation, whereas moderately high dietary fat with extra sucrose is necessary and sufficient for hepatosteatosis advancement to steatohepatitis. Hence, liver and adipose tissues respond to dietary fat and sucrose in opposite manners, yet both macronutrients are contributing factors to metabolic diseases.<\/jats:p>","DOI":"10.3390\/molecules25194369","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T03:03:39Z","timestamp":1600916619000},"page":"4369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Distinct Influence of Hypercaloric Diets Predominant with Fat or Fat and Sucrose on Adipose Tissue and Liver Inflammation in Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Ca\u00edque S. M.","family":"Fonseca","sequence":"first","affiliation":[{"name":"Department of Pathology, Metabolic Diseases Research Center, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"},{"name":"Grupo de Pesquisa em Doen\u00e7as Metab\u00f3licas, Faculdade Tiradentes de Jaboat\u00e3o dos Guararapes, Sociedade de Educa\u00e7\u00e3o Tiradentes, Jaboat\u00e3o dos Guararapes, Pernambuco 54410-100, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua E.","family":"Basford","sequence":"additional","affiliation":[{"name":"Department of Pathology, Metabolic Diseases Research Center, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"Kuhel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Metabolic Diseases Research Center, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eddy S.","family":"Konaniah","sequence":"additional","affiliation":[{"name":"Department of Pathology, Metabolic Diseases Research Center, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James G.","family":"Cash","sequence":"additional","affiliation":[{"name":"Department of Pathology, Metabolic Diseases Research Center, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2581-9218","authenticated-orcid":false,"given":"Vera L. M.","family":"Lima","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Lip\u00eddeos, Departamento de Bioqu\u00edmica, Centro de Bioci\u00eancias, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Y.","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Pathology, Metabolic Diseases Research Center, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0140-6736(10)62037-5","article-title":"National, regional, and global trends in body-mass index since 1980: Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9\u00b71 million participants","volume":"377","author":"Finucane","year":"2011","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.jamcollsurg.2008.08.022","article-title":"Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with obesity: Findings from the National Health and Nutrition Examination Survey, 1999 to 2004","volume":"207","author":"Nguyen","year":"2008","journal-title":"J. Am. Coll. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2013.09.019","article-title":"Obesity and liver disease. The epidemic of the twenty-first century","volume":"18","author":"Corey","year":"2014","journal-title":"Clin. Liver Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bertola, A., Bonnafous, S., Anty, R., Patouraux, S., Saint-Paul, M.C., Iannelli, A., Gugenheim, J., Barr, J., Mato, J.M., and Le Marchand-Brustel, Y. (2010). Hepatic expression patterns of inflammatory and immune response genes associated with obesity and NASH in morbidly obese patients. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013577"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E262","DOI":"10.1152\/ajpendo.00271.2013","article-title":"Metabolic remodeling of white adipose tissue in obesity","volume":"307","author":"Cummins","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/obr.12407","article-title":"Obesity is an independent risk factor for non-alcoholic fatty liver disease: Evidence from a meta-analysis of 21 cohort studies","volume":"17","author":"Li","year":"2016","journal-title":"Obes. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/cld.674","article-title":"Nonobese nonalcoholic fatty liver disease","volume":"10","author":"Aby","year":"2017","journal-title":"Clin. Liver Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1055\/s-0028-1091978","article-title":"The epidemiology of nonalcoholic fatty liver disease: A global perspective","volume":"28","author":"Lazo","year":"2008","journal-title":"Semin. Liver Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1365-2036.2011.04724.x","article-title":"Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults","volume":"34","author":"Vernon","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149","DOI":"10.5009\/gnl.2012.6.2.149","article-title":"NASH is an inflammatory disorder: Pathogenic, prognostic and therapeutic implications","volume":"6","author":"Farrell","year":"2012","journal-title":"Gut Liver"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1381\/096089202321144577","article-title":"Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery","volume":"12","author":"Gholam","year":"2002","journal-title":"Obes. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/hep.23719","article-title":"Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites","volume":"52","year":"2010","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2147\/DMSO.S198968","article-title":"The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disorders","volume":"12","author":"Mai","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.mcna.2017.08.009","article-title":"Dietary management of obesity: Cornerstones of healthy eating patterns","volume":"102","author":"Smethers","year":"2018","journal-title":"Med. Clin. N. Am."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e7666","DOI":"10.1136\/bmj.e7666","article-title":"Effect of reducing total fat intake on body weight: Systematic review and meta-analysis of randomised controlled trials and cohort studies","volume":"345","author":"Hooper","year":"2012","journal-title":"BMJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1056\/NEJMoa0804748","article-title":"Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates","volume":"360","author":"Sacks","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Fogelholm, M., Anderssen, S., Gunnarsdottir, I., and Lahti-Koski, M. (2012). Dietary macronutrients and food consumption as determinants of long-term weight change in adult populations: A systematic literature review. Food Nutr. Res., 56.","DOI":"10.3402\/fnr.v56i0.19103"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ecl.2016.04.009","article-title":"The role of macronutrient content in the diet for weight management","volume":"45","author":"Bray","year":"2016","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.psc.2011.08.004","article-title":"Dietary approaches to the treatment of obesity","volume":"34","author":"Makris","year":"2011","journal-title":"Psychiatr. Clin. N. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1017\/S0007114513000548","article-title":"Very low carbohydrate ketogenic diet v. low fat diet for long term weight loss: A meta-analysis of randomised controlled trials","volume":"110","author":"Bueno","year":"2013","journal-title":"Br. J. Nutr"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1017\/S0007114515004699","article-title":"Effects of low carbohydrate diets v. low fat diets on body weight and cardiovascular risk factors: A meta-analysis of randomised controlled trials","volume":"115","author":"Mansoor","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sackner-Bernstein, J., Kanter, D., and Kaul, S. (2015). Dietary intervention for overweight and obese adults: Comparison of low carbohydrate and low fat diets. A meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139817"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.3945\/ajcn.2009.29099","article-title":"Intake of carbohydrates compared with intake of saturated fatty acids and risk of myocardial infarction: Importance of the glycemic index","volume":"91","author":"Jakobsen","year":"2010","journal-title":"Am. J. Clin. Nutr"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"147","DOI":"10.7326\/0003-4819-153-3-201008030-00005","article-title":"Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: A randomized trial","volume":"153","author":"Foster","year":"2010","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1038\/s41366-018-0298-4","article-title":"Personalized nutrition: Pretreatment glucose metabolism determines individual long-term weight loss responsiveness in individuals with obesity on low carbohydrate versus low fat diet","volume":"43","author":"Hjorth","year":"2019","journal-title":"Int. J. Obes."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.molmet.2014.09.006","article-title":"Defective insulin secretory response to intravenous glucose in C57BL\/6J compared to C57BL\/6N mice","volume":"3","author":"Fergusson","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1194\/jlr.M500294-JLR200","article-title":"Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans","volume":"46","author":"Cinti","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.expneurol.2015.04.010","article-title":"The influence of the cage environment on rodent physiology and behavior: Implications for reproducibility of pre-clinical rodent research","volume":"270","author":"Toth","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.cmet.2017.02.001","article-title":"Integrative physiology: At the crossroads of nutrition, microbiota, animal physiology, and human health","volume":"25","author":"Leulier","year":"2017","journal-title":"Cell Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/00041433-200106000-00012","article-title":"Leptin and its role in lipid metabolism","volume":"12","author":"Hynes","year":"2001","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1515\/hmbci-2013-0053","article-title":"The role of leptin\/adiponectin ratio in metabolic syndrome and diabetes","volume":"18","year":"2014","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2174\/157339508784325046","article-title":"Leptin and inflammation","volume":"4","author":"Iikuni","year":"2008","journal-title":"Curr. Immunol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cca.2007.01.026","article-title":"Adiponectin as an anti-inflammatory factor","volume":"380","author":"Ouchi","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.cell.2013.01.041","article-title":"The origins and drivers of insulin resistance","volume":"152","author":"Johnson","year":"2013","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"256","DOI":"10.18632\/aging.100738","article-title":"High fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL\/6J mice","volume":"7","author":"Sheedfar","year":"2015","journal-title":"Aging"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/S0016-5085(98)70599-2","article-title":"Steatohepatitis: A tale of two hits","volume":"114","author":"Day","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/hep.22363","article-title":"Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis","volume":"48","author":"Wouters","year":"2008","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/hep.25789","article-title":"Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis","volume":"57","author":"Savard","year":"2013","journal-title":"Hepatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/hep.23797","article-title":"High-fructose, medium chain trans fat diet induces liver fibrosis and elevates plasma coenzyme Q9 in a novel murine model of obesity and nonalcoholic steatohepatitis","volume":"52","author":"Kohli","year":"2010","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/MOL.0b013e3283613bca","article-title":"Adverse metabolic effects of dietary fructose: Results from the recent epidemiological, clinical, and mechanistic studies","volume":"24","author":"Stanhope","year":"2013","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.atherosclerosis.2020.05.002","article-title":"Dietary sucrose induces metabolic inflammation and atherosclerotic cardiovascular diseases more than dietary fat in Ldlr\u2212\/\u2212ApoB100\/100 mice","volume":"304","author":"Perazza","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"174","DOI":"10.2174\/138945008783755629","article-title":"Lipoprotein size and susceptibility to atherosclerosis\u2014Insights from genetically modified mouse models","volume":"9","author":"Veniant","year":"2008","journal-title":"Curr. Drug Targets"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1074\/jbc.RA119.012361","article-title":"Hepatic HAX-1 inactivation prevents metabolic diseases by enhancing mitochondrial activity and bile salt export","volume":"295","author":"Alogaili","year":"2020","journal-title":"J. Biol. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/19\/4369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:12:50Z","timestamp":1760177570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/19\/4369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,23]]},"references-count":43,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["molecules25194369"],"URL":"https:\/\/doi.org\/10.3390\/molecules25194369","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2020,9,23]]}}}