{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:34:26Z","timestamp":1792204466707,"version":"4.4.0"},"reference-count":63,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T00:00:00Z","timestamp":1720915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["21K11608"],"award-info":[{"award-number":["21K11608"]}]},{"name":"Japan Society for the Promotion of Science","award":["24K14638"],"award-info":[{"award-number":["24K14638"]}]},{"name":"Japan Society for the Promotion of Science","award":["23K24765"],"award-info":[{"award-number":["23K24765"]}]},{"name":"Japan Association for Diabetes Education and Care","award":["21K11608"],"award-info":[{"award-number":["21K11608"]}]},{"name":"Japan Association for Diabetes Education and Care","award":["24K14638"],"award-info":[{"award-number":["24K14638"]}]},{"name":"Japan Association for Diabetes Education and Care","award":["23K24765"],"award-info":[{"award-number":["23K24765"]}]},{"name":"Fujita Health University","award":["21K11608"],"award-info":[{"award-number":["21K11608"]}]},{"name":"Fujita Health University","award":["24K14638"],"award-info":[{"award-number":["24K14638"]}]},{"name":"Fujita Health University","award":["23K24765"],"award-info":[{"award-number":["23K24765"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>(1) Background: Proglucagon-derived peptides (PDGPs) including glucagon (Gcg), GLP-1, and GLP-2 regulate lipid metabolism in the liver, adipocytes, and intestine. However, the mechanism by which PGDPs participate in alterations in lipid metabolism induced by high-fat diet (HFD) feeding has not been elucidated. (2) Methods: Mice deficient in PGDP (GCGKO) and control mice were fed HFD for 7 days and analyzed, and differences in lipid metabolism in the liver, adipose tissue, and duodenum were investigated. (3) Results: GCGKO mice under HFD showed lower expression levels of the genes involved in free fatty acid (FFA) oxidation such as Hsl, Atgl, Cpt1a, Acox1 (p &lt; 0.05), and Ppar\u03b1 (p = 0.05) mRNA in the liver than in control mice, and both FFA and triglycerides content in liver and adipose tissue weight were lower in the GCGKO mice. On the other hand, phosphorylation of hormone-sensitive lipase (HSL) in white adipose tissue did not differ between the two groups. GCGKO mice under HFD exhibited lower expression levels of Ppar\u03b1 and Cd36 mRNA in the duodenum as well as increased fecal cholesterol contents compared to HFD-controls. (4) Conclusions: GCGKO mice fed HFD exhibit a lesser increase in hepatic FFA and triglyceride contents and adipose tissue weight, despite reduced \u03b2-oxidation in the liver, than in control mice. Thus, the absence of PGDP prevents dietary-induced fatty liver development due to decreased lipid uptake in the intestinal tract.<\/jats:p>","DOI":"10.3390\/nu16142270","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T08:35:17Z","timestamp":1721032517000},"page":"2270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impaired Fat Absorption from Intestinal Tract in High-Fat Diet Fed Male Mice Deficient in Proglucagon-Derived Peptides"],"prefix":"10.3390","volume":"16","author":[{"given":"Koki","family":"Nishida","sequence":"first","affiliation":[{"name":"Departments of Endocrinology, Diabetes and Metabolism, Fujita Health University School of Medicine, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Ueno","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology, Diabetes and Metabolism, Fujita Health University School of Medicine, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9099-3493","authenticated-orcid":false,"given":"Yusuke","family":"Seino","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology, Diabetes and Metabolism, Fujita Health University School of Medicine, Toyoake 470-1192, Japan"},{"name":"Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto 604-8436, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihomi","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology, Diabetes and Metabolism, Fujita Health University School of Medicine, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Murao","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology, Diabetes and Metabolism, 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake 470-1192, Japan"},{"name":"Department of Medical Research on Prebiotics and Probiotics, Fujita Health University, Toyoake 470-1101, Japan"},{"name":"BIOSIS Lab. 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Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/0005-2760(67)90057-4","article-title":"Effect of glucagon on lipid and glycogen content of the perfused rat liver","volume":"144","author":"Penhos","year":"1967","journal-title":"Biochim. Et Biophys. Acta BBA Lipids Lipid Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"574","DOI":"10.2337\/diab.24.6.574","article-title":"Gluconeogenesis from alanine in normal postabsortive man.Intrahepatic stimulatory effect of glucagon","volume":"24","author":"Chiasson","year":"1975","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1172\/JCI111272","article-title":"Effects of glucagon on plasma amino acids","volume":"73","author":"Boden","year":"1984","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Janah, L., Kjeldsen, S., Galsgaard, K.D., Winther-S\u00f8rensen, M., Stojanovska, E., Pedersen, J., Knop, F.K., Holst, J.J., and Wewer Albrechtsen, N.J. (2019). Glucagon Receptor Signaling and Glucagon Resistance. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133314"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1042\/bj2640093","article-title":"Induction of ketogenesis and fatty acid oxidation by glucagon and cyclic AMP in induced hepatocytes from rabbit fetuses","volume":"264","author":"Kohl","year":"1989","journal-title":"Biochem. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0022-2275(20)40346-3","article-title":"Effect of hormones on lipolysis and esterification of free fatty acid during incubation of adipose tissue in vitro","volume":"4","author":"Vaughan","year":"1963","journal-title":"J. Lipid Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S0021-9258(18)96968-1","article-title":"Metabolism of isolated fat cells. 3. The similar inhibitory action of phospholipase C (Clostridium perfringens alpha toxin) and of insulin on lipolysis stimulated by lipolytic hormones and theophylline","volume":"241","author":"Rodbell","year":"1966","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1055\/s-0028-1096783","article-title":"Lipolytic effect of intra-arterial injection of glucagon in man","volume":"3","author":"Pozza","year":"1971","journal-title":"Horm. Metab. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0022-2275(20)36889-9","article-title":"Hypolipemic action of glucagon in experimental endogenous lipemia in the rat","volume":"14","author":"Eaton","year":"1973","journal-title":"J. Lipid Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0026-0495(74)90061-4","article-title":"Effects of glucagon on plasma lipids in different types of primary hyperlipoproteinemia","volume":"23","author":"Aubry","year":"1974","journal-title":"Metabolism"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0005-2760(88)90283-4","article-title":"Effect of chronic glucagon administration on cholesterol and bile acid metabolism","volume":"963","author":"Guettet","year":"1988","journal-title":"Biochim. Et Biophys. Acta BBA Lipids Lipid Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1042\/bj2620425","article-title":"Glucagon, cyclin AMP and adrenaline stimulate the degradation of low-density lipoprotein by culture rat hepatocytes","volume":"262","author":"Brown","year":"1989","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.2337\/db17-1502","article-title":"Glucagon Receptor Signaling Regulates Energy Metabolism via Hepatic Farnesoid X Receptor and Fibroblast Growth Factor 21","volume":"67","author":"Kim","year":"2018","journal-title":"Diabetes"},{"key":"ref_15","first-page":"e141323","article-title":"Glucagon receptor signaling regulates weight loss via central KLB receptor complexes","volume":"6","author":"Nason","year":"2021","journal-title":"JCI Insight"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1172\/JCI20911","article-title":"Hepatic and glucagon-like peptide-1-mediated reversal of diabetes by glucagon receptor anti-sense oligonucleotide inhibitors","volume":"113","author":"Sloop","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/j.celrep.2018.01.065","article-title":"Glucagon Receptor Antagonism Improves Glucose Metabolism and Cardiac Function by Promoting AMP-Mediated Protein Kinase in Diabetic Mice","volume":"22","author":"Sharma","year":"2018","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s00125-006-0481-3","article-title":"Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia","volume":"50","author":"Conarello","year":"2007","journal-title":"Diabetologia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1007\/s00125-016-3935-2","article-title":"Endogenous GIP ameliorates impairment of insulin secretion in proglucagon-deficient mice under moderate beta cell damage induced by streptozotocin","volume":"59","author":"Iida","year":"2016","journal-title":"Diabetologia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1194\/jlr.M035592","article-title":"Effects of small interfering RNA-mediated hepatic glucagon receptor inhibition on lipid metabolism in db\/db mice","volume":"54","author":"Han","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1194\/jlr.M060897","article-title":"Glucagon receptor antagonism induces increased cholesterol absorption","volume":"56","author":"Guan","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1172\/JCI43615","article-title":"Dual elimination of the glucagon and GLP-1 receptors in mice reveals plasticity in the incretin axis","volume":"121","author":"Ali","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1172\/JCI97233","article-title":"Discovery, characterization, and clinical development of the glucagon-like peptides","volume":"127","author":"Drucker","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2337\/db12-0202","article-title":"GLP-1 and GLP-2 as yin and yang of intestinal lipoprotein production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin-resistant states","volume":"62","author":"Hein","year":"2013","journal-title":"Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/s00125-009-1611-5","article-title":"The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice","volume":"53","author":"Hsieh","year":"2010","journal-title":"Diabetologia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1053\/j.gastro.2009.05.051","article-title":"Glucagon-like peptide-2 increases intestinal lipid absorption and chylomicron production via CD36","volume":"137","author":"Hsieh","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Takagi, Y., Kinoshita, K., Ozaki, N., Seino, Y., Murata, Y., Oshida, Y., and Hayashi, Y. (2015). Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138322"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ueno, S., Seino, Y., Hidaka, S., Maekawa, R., Takano, Y., Yamamoto, M., Hori, M., Yokota, K., Masuda, A., and Himeno, T. (2022). High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides. Nutrients, 14.","DOI":"10.3390\/nu14050975"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1210\/me.2009-0296","article-title":"Mice deficient for glucagon gene-derived peptides display normoglycemia and hyperplasia of islet \u03b1-cells but not of intestinal L-cells","volume":"23","author":"Hayashi","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2337\/db11-0739","article-title":"Remodeling of hepatic metabolism and hyperaminoacidemia in mice deficient in proglucagon-derived peptides","volume":"61","author":"Watanabe","year":"2012","journal-title":"Diabetes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e140418","DOI":"10.1172\/jci.insight.140418","article-title":"Hematopoietic cell- versus enterocyte-derived dipeptidyl peptidase-4 differentially regulates triglyceride excursion in mice","volume":"5","author":"Varin","year":"2020","journal-title":"JCI Insight"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15638","DOI":"10.1074\/jbc.RA119.009230","article-title":"C1q\/TNF-related protein 2 (CTRP2) deletion promotes adipose tissue lipolysis and hepatic triglyceride secretion","volume":"294","author":"Lei","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Masuda, A., Seino, Y., Murase, M., Hidaka, S., Shibata, M., Takayanagi, T., Sugimura, Y., Hayashi, Y., and Suzuki, A. (2019). Short-term high-starch, low-protein diet induces reversible increase in \u03b2-cell mass independent of body weight gain in mice. Nutrients, 11.","DOI":"10.3390\/nu11051045"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Takahashi, S., Tomita, J., Nishioka, K., Hisada, T., and Nishijima, M. (2014). Development of a prokaryotic universal primer for simultaneous analysis of Bacteria and Archaea using next-generation sequencing. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105592"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Takahashi, H., Fujii, T., Yamakawa, S., Yamada, C., Fujiki, K., Kondo, N., Funasaka, K., Hirooka, Y., and Tochio, T. (2023). Combined oral intake of short and long fructans alters the gut microbiota in food allergy model mice and contributes to food allergy pre-vention. BMC Microbiol., 23.","DOI":"10.1186\/s12866-023-03021-6"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1574-6941.2009.00671.x","article-title":"Comparative assessment of human and farm animal faecal microbiota using real-time quantitative PCR","volume":"68","author":"Furet","year":"2009","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41574-022-00794-0","article-title":"The gut microbiota in obesity and weight management: Microbes as friends or foe?","volume":"19","author":"Hul","year":"2023","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6584","DOI":"10.1038\/s41467-023-42334-y","article-title":"Gut insulin action protects from hepatocarcinogenesis in diabetic mice comorbid with nonalcoholic steatohepatitis","volume":"14","author":"Soeda","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9167","DOI":"10.1038\/s41598-021-88612-x","article-title":"Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms","volume":"11","author":"Kato","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15582","DOI":"10.1038\/s41598-019-52103-x","article-title":"Metabolic and gut microbiome changes following GLP-1 or dual GLP-1\/GLP-2 receptor agonist treatment in di-et-induced obese mice","volume":"9","author":"Madsen","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_41","first-page":"83","article-title":"Hepatic steatosis: A role for de novo lipogenesis and the transcription factor SREBP-1c","volume":"2","author":"Foufelle","year":"2010","journal-title":"Diabetes Obes. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.2337\/db07-0907","article-title":"Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity","volume":"56","author":"Koonen","year":"2007","journal-title":"Diabetes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"G855","DOI":"10.1152\/ajpgi.00434.2009","article-title":"Insulin- and leptin-regulated fatty acid uptake plays a key causal role in hepatic steatosis in mice with intact leptin signaling but not in ob\/ob or db\/db mice","volume":"299","author":"Ge","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1210\/en.2015-1866","article-title":"Hepatocyte-Specific Disruption of CD36 Attenuates Fatty Liver and Improves Insulin Sensitivity in HFD-Fed Mice","volume":"157","author":"Wilson","year":"2016","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JOE-16-0513","article-title":"Hepatic lipid accumulation: Cause and consequence of dysregulated glucoregulatory hormones","volume":"234","author":"Geisler","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1136\/gutjnl-2015-310798","article-title":"Liver PPAR\u03b1 is crucial for whole-body fatty acid homeostasis and is protective against NAFLD","volume":"65","author":"Montagner","year":"2016","journal-title":"Gut"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"R733","DOI":"10.1152\/ajpregu.00153.2019","article-title":"Loss of hepatic PPAR\u03b1 promotes inflammation and serum hyperlipidemia in diet-induced obesity","volume":"317","author":"Stec","year":"2019","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, J., MacDougall, M.L., McDowell, M.T., Xi, L., Wei, R., Zavadoski, W.J., Molloy, M.P., Baker, J.D., Kuhn, M., and Cabrera, O. (2011). Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: Im-plications on anti-glucagon therapies for diabetes. BMC Genom., 12.","DOI":"10.1186\/1471-2164-12-281"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101639","DOI":"10.1016\/j.molmet.2022.101639","article-title":"Glucagon receptor antagonism impairs and glucagon receptor agonism enhances triglycerides metabolism in mice","volume":"66","author":"Galsgaard","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41586-020-2074-6","article-title":"Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis","volume":"579","author":"Perry","year":"2020","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19034","DOI":"10.1074\/jbc.M115.640292","article-title":"Hyperinsulinemia Enhances Hepatic Expression of the Fatty Acid Transporter Cd36 and Provokes Hepatosteatosis and Hepatic Insulin Resistance","volume":"290","author":"Steneberg","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/jdi.14032","article-title":"Blockade of glucagon increases muscle mass and alters fiber type composition in mice deficient in proglucagon-derived peptides","volume":"14","author":"Ueno","year":"2023","journal-title":"J. Diabetes Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E389","DOI":"10.1152\/ajpendo.00078.2022","article-title":"Glucagon receptor signaling at white adipose tissue does not regulate lipolysis","volume":"323","author":"Vasileva","year":"2022","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7940","DOI":"10.1038\/ncomms8940","article-title":"A hepatic amino acid\/mTOR\/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals","volume":"6","author":"Uno","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1038\/ncomms3316","article-title":"Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization","volume":"4","author":"Izumida","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41467-017-02488-y","article-title":"GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose","volume":"9","author":"Iwasaki","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e136907","DOI":"10.1172\/jci.insight.136907","article-title":"Loss of Glp2r signaling activates hepatic stellate cells and exacerbates diet-induced steatohepatitis in mice","volume":"5","author":"Fuchs","year":"2020","journal-title":"JCI Insight"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3340","DOI":"10.1210\/en.2018-00416","article-title":"GLP-2 Dysregulates Hepatic Lipoprotein Metabolism, Inducing Fatty Liver and VLDL Overproduction in Male Hamsters and Mice","volume":"159","author":"Taher","year":"2018","journal-title":"Endocrinology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1002\/jcp.25039","article-title":"GLP-2 as Beneficial Factor in the Glucose Homeostasis in Mice Fed a High Fat Diet","volume":"230","author":"Baldassano","year":"2015","journal-title":"J. Cell Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7031","DOI":"10.1038\/s41467-021-27133-7","article-title":"Dietary excess regulates absorption and surface of gut epithelium through intestinal PPAR\u03b1","volume":"12","author":"Altirriba","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.cmet.2008.09.008","article-title":"The glucagon receptor is required for the adaptive metabolic response to fasting","volume":"8","author":"Longuet","year":"2008","journal-title":"Cell Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101797","DOI":"10.1016\/j.molmet.2023.101797","article-title":"Isoxanthohumol improves obesity and glucose metabolism via inhibiting intestinal lipid absorption with a bloom of Akkermansia muciniphila in mice","volume":"77","author":"Watanabe","year":"2023","journal-title":"Mol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1017\/S0007114519001909","article-title":"The association between gut microbiota composition and BMI in Chinese male college students, as analysed by next-generation sequencing","volume":"122","author":"Lv","year":"2019","journal-title":"Br. J. 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