title: Liraglutide prevents fast weight gain and β-cell dysfunction in male catch-up growth rats.
abstract: We reported recently that after a nutritional growth retardation, rats showed significant weight gain, central fat accumulation, dyslipidemia, and β-cell dysfunction during a catch-up growth (CUG) phase. Here, we investigated whether glucagon-like peptide-1 (GLP-1) ameliorated the rapid weight gain, central fat deposition, and β-cell dysfunction during the CUG in rats. Sixty-four male Sprague Dawley rats were stratified into four groups including normal control group, CUG group, catch-up growth with liraglutide treatment group, and catch-up growth with liraglutide and exendin 9-39 treatment group. Energy intake, body weight, and body length were monitored. Fat mass percentage was analyzed by dual energy X-ray absorptiometry scan. Plasma triglyceride and non-esterified fatty acid were measured. The β-cell mass was analyzed by morphometric analysis and signaling molecules were examined by Western blot and real-time PCR. Insulin secretion capability was evaluated by hyperglycemic clamp test. Liraglutide prevented weight gain and improved lipid and glucose metabolism in rats under CUG conditions, which were associated with reduced fasting insulin levels and improved glucose-stimulated insulin secretion. Improved β-cell function is found to be associated with increased β-cell replication as determined by β-cell density and insulin-Ki67 dual staining. Furthermore, liraglutide increased islet pancreatic duodenal homeobox-1 (Pdx-1) and B-cell lymphoma-2 transcript and protein expression, and reduced Procaspase-3 transcript and Caspase-3 p11 subunit protein expression, suggesting that expression of Pdx-1 and reduction of apoptosis may be the mechanisms involved. The therapeutic effects were attenuated in rats co-administered with exendin 9-39, suggesting a GLP-1 receptor-dependent mechanism. These studies revealed that incretin therapy effectively prevented fast weight gain and β-cell dysfunction in rats under conditions of nutrition restriction followed by nutrition excess, which is in part due to enhanced functional β-cell mass and insulin secretory capacity.
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China Division of Endocrinology and Metabolism, The Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario M2J4A6, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China Department of Endocrinology, Soochow University Affiliated Children's Hospital, Soochow University, Suzhou, Jiangsu 215000, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Deng
authors.affiliation: Division of Endocrinology and Metabolism, The Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario M2J4A6, Canada Departments of Physiology and Medicine, University of Toronto, Toronto M2J4A6, Canada.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Jiao-Yue
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China cheria.chen@126.com.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Chen
mesh_terms: D000818:Animals; D031204:Caloric Restriction / Q000009:adverse effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054795:Incretins / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D056128:Obesity, Abdominal / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
chemical_list: D005230:Fatty Acids, Nonesterified; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D015534:Trans-Activators; D014280:Triglycerides; C084010:pancreatic and duodenal homeobox 1 protein; D000069450:Liraglutide
keywords: Catch-up growth; GLP-1; liraglutide; β-cell dysfunction