Beyond thermoregulation: metabolic function of cetacean blubber in migrating bowhead and beluga whales.
*Lipid Metabolism; Adipose Tissue/*metabolism; Aging/metabolism; Amino Acid Sequence; Animals; Base Sequence; Beluga Whale/*physiology; Blubber; Body Temperature Regulation; Bowhead whale; Bowhead Whale/*physiology; Development; Female; Humans; Inbred C57BL; Leptin; Leptin/genetics; Leptin/genetics/metabolism; Lipase/genetics; Long-Evans; Male; Metabolic activity; Mice; Rats; Receptors; Seasons
The processes of lipid deposition and utilization, via the gene leptin (Lep), are poorly understood in taxa with varying degrees of adipose storage. This study examines how these systems may have adapted in marine aquatic environments inhabited by cetaceans. Bowhead (Balaena mysticetus) and beluga whales (Delphinapterus leucas) are ideal study animals-they possess large subcutaneous adipose stores (blubber) and undergo bi-annual migrations concurrent with variations in food availability. To answer long-standing questions regarding how (or if) energy and lipid utilization adapted to aquatic stressors, we quantified variations in gene transcripts critical to lipid metabolism related to season, age, and blubber depth. We predicted leptin tertiary structure conservation and assessed inter-specific variations in Lep transcript numbers between bowheads and other mammals. Our study is the first to identify seasonal and age-related variations in Lep and lipolysis in these cetaceans. While Lep transcripts and protein oscillate with season in adult bowheads reminiscent of hibernating mammals, transcript levels reach up to 10 times higher in bowheads than any other mammal. Data from immature bowheads are consistent with the hypothesis that short baleen inhibits efficient feeding. Lipolysis transcripts also indicate young Fall bowheads and those sampled during Spring months limit energy utilization. These novel data from rarely examined species expand the existing knowledge and offer unique insight into how the regulation of Lep and lipolysis has adapted to permit seasonal deposition and maintain vital blubber stores.
Ball H C; Londraville R L; Prokop J W; George John C; Suydam R S; Vinyard C; Thewissen J G M; Duff R J
Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology
2017
2017-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00360-016-1029-6" target="_blank" rel="noreferrer noopener">10.1007/s00360-016-1029-6</a>
Interplay between obesity and aging on myocardial geometry and function: Role of leptin-STAT3-stress signaling
Background: Uncorrected obesity facilitates premature aging and cardiovascular anomalies. This study examined the interaction between obesity and aging on cardiac remodeling and contractile function.
Methods: Cardiac echocardiographic geometry, function, morphology, intracellular Ca2+ handling, oxidative stress (DHE fluorescence), STAT3 and stress signaling were evaluated in young (3-mo) and old (12- and 18-mo) lean and leptin deficient ob/ob obese mice. Cardiomyocytes from young and old lean and ob/ob mice were treated with leptin (1 nM) for 4 h in vitro prior to assessment of mechanical and biochemical properties. High fat diet (45% calorie from fat) and the leptin receptor mutant db/db obese mice at young and old age were evaluated for comparison.
Results: Our results displayed reduced survival in ob/ob mice. Obesity but less likely older age dampened echocardiographic, geometric, cardiomyocyte function and intracellular Ca2+ properties, elevated O2- and p47phox NADPH oxidase levels with a more pronounced geometric change at older age. Immunoblot analysis revealed elevated p47phox NADPH oxidase and dampened phosphorylation of STAT3, with a more pronounced response in old ob/ob mice, the effects were restored by leptin. Obesity and aging inhibited phosphorylation of Akt, eNOS, AMPK, and p38 while promoting phosphorylation of JNK and IκB. Leptin reconciled cardiomyocyte dysfunction, O2- yield, p47phox upregulation, STAT3 dephosphorylation and stress signaling in ob/ob mice although its action on stress signaling cascades were lost at old age. High fat diet-induced and db/db obesity displayed aging-associated cardiomyocyte anomalies reminiscent of ob/ob model albeit lost leptin response.
Conclusions: Our data suggest disparate age-associated obesity response in cardiac remodeling and contractile dysfunction due to phosphorylation of Akt, eNOS and stress signaling-related oxidative stress.
Wei Jin
Fei Tu
Feng Dong
Qinqin Deng
Miyesaier Abudureyimu
Wei Yu
Guo-Jun Cai
Jian-Ming Pei
Zhaohui Pei
Jun Ren
Biochim Biophys Acta Gen Subj
. 2023 Feb;1867(2):130281. doi: 10.1016/j.bbagen.2022.130281. Epub 2022 Nov 18.
2022
English
Leptin in Atherosclerosis: Focus on Macrophages, Endothelial and Smooth Muscle Cells.
Humans; atherosclerosis; Animals; endothelial cells; macrophages; vascular smooth muscle cells; Leptin/metabolism; Atherosclerosis/metabolism; Diabetes Mellitus/metabolism; Endothelial Cells/metabolism; hyperleptinemia; Macrophages/metabolism; Myocytes Smooth Muscle/metabolism; Obesity/metabolism; ADIPOSE tissue physiology; LEPTIN; LEPTIN receptors; MACROPHAGES; MUSCLE cells; SMOOTH muscle
Increasing adipose tissue mass in obesity directly correlates with elevated circulating leptin levels. Leptin is an adipokine known to play a role in numerous biological processes including regulation of energy homeostasis, inflammation, vascular function and angiogenesis. While physiological concentrations of leptin may exhibit multiple beneficial effects, chronically elevated pathophysiological levels or hyperleptinemia, characteristic of obesity and diabetes, is a major risk factor for development of atherosclerosis. Hyperleptinemia results in a state of selective leptin resistance such that while beneficial metabolic effects of leptin are dampened, deleterious vascular effects of leptin are conserved attributing to vascular dysfunction. Leptin exerts potent proatherogenic effects on multiple vascular cell types including macrophages, endothelial cells and smooth muscle cells; these effects are mediated via an interaction of leptin with the long form of leptin receptor, abundantly expressed in atherosclerotic plaques. This review provides a summary of recent in vivo and in vitro studies that highlight a role of leptin in the pathogenesis of atherosclerotic complications associated with obesity and diabetes.
Raman P; Khanal S
International Journal Of Molecular Sciences
2021
2021-05-21
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.3390/ijms22115446" target="_blank" rel="noreferrer noopener">10.3390/ijms22115446</a>
The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.
*Rats; Animal; Animals; Aortic Aneurysm; Atherosclerosis/pathology; Blood Glucose/metabolism; Blood Vessels/pathology; Body Weight; Collagen/biosynthesis; Cysts/*genetics/pathology; Disease Models; hypoxia; Hypoxia; Inbred Strains; leptin; Lipids/blood; Male; metabolic syndrome; Metabolic Syndrome/*genetics/pathology; Necrosis; Proteoglycans/biosynthesis; Rats; rodent model; Thoracic/*genetics/pathology
Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia.NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN.
Pung Yuh Fen; Chilian William M; Bennett Martin R; Figg Nichola; Kamarulzaman Mohd Hamzah
American journal of physiology. Heart and circulatory physiology
2017
2017-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpheart.00653.2016" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00653.2016</a>
TSP-1 (thrombospondin-1) deficiency protects APOE(-/-) mice against leptin-induced atherosclerosis.
atherosclerosis; leptin; obesity; smooth muscle; thrombospondins
OBJECTIVE: Hyperleptinemia, hallmark of obesity, is a putative pathophysiologic trigger for atherosclerosis. We previously reported a stimulatory effect of leptin on TSP-1 (thrombospondin-1) expression, a proatherogenic matricellular protein implicated in atherogenesis. However, a causal role of TSP-1 in leptin-driven atherosclerosis remains unknown. Approach and Results: Seventeen-weeks-old ApoE(-/-) and TSP-1(-/-)/ApoE(-/-) double knockout mice, on normocholesterolemic diet, were treated with or without murine recombinant leptin (5 µg/g bwt, IP) once daily for 3 weeks. Using aortic root morphometry and en face lesion assay, we found that TSP-1 deletion abrogated leptin-stimulated lipid-filled lesion burden, plaque area, and collagen accumulation in aortic roots of ApoE(-/-) mice, shown via Oil red O, hematoxylin and eosin, and Masson trichrome staining, respectively. Immunofluorescence microscopy of aortic roots showed that TSP-1 deficiency blocked leptin-induced inflammatory and smooth muscle cell abundance as well as cellular proliferation in ApoE(-/-) mice. Moreover, these effects were concomitant to changes in VLDL (very low-density lipoprotein)-triglyceride and HDL (high-density lipoprotein)-cholesterol levels. Immunoblotting further revealed reduced vimentin and pCREB accompanied with augmented smooth muscle-myosin heavy chain expression in aortic vessels of leptin-treated double knockout versus leptin-treated ApoE(-/-); also confirmed in aortic smooth muscle cells from the mice genotypes, incubated ± leptin in vitro. Finally, TSP-1 deletion impeded plaque burden in leptin-treated ApoE(-/-) on western diet, independent of plasma lipid alterations. CONCLUSIONS: The present study provides evidence for a protective effect of TSP-1 deletion on leptin-stimulated atherogenesis. Our findings suggest a regulatory role of TSP-1 on leptin-induced vascular smooth muscle cell phenotypic transition and inflammatory lesion invasion. Collectively, these results underscore TSP-1 as a potential target of leptin-induced vasculopathy.
Ganguly R; Khanal S; Mathias A; Gupta S; Lallo J; Sahu S; Ohanyan VA; Patel A; Storm K; Datta S; Raman P
Arteriosclerosis, Thrombosis, and Vascular Biology
2020
2020-12-17
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1161/ATVBAHA.120.314962" target="_blank" rel="noreferrer noopener">10.1161/ATVBAHA.120.314962</a>