Leptin attenuates respiratory complications associated with the obese phenotype

Tankersley, Clarke G.; O’Donnell, Christopher P.; Daood, Monica J.; Watchko, Jon F.; Mitzner, Wayne; Schwartz, Alan R.; Smith, Philip L.

doi:10.1152/jappl.1998.85.6.2261

Cited by 151 publications

(118 citation statements)

References 37 publications

(42 reference statements)

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…One such change is the increase in the functional demand on (i) postural muscles, such as SOL, that are required to support a proportionally greater body mass against gravity; (ii) locomotor muscles, such as EDL, that must overcome the proportionally greater inertia of the limbs during movement; and (iii) muscles of ventilation, such as the accessory SM, 10 that must cope with an increased work of breathing associated with obesity. 4 Earlier work investigating respiratory muscles from genetically obese rodents supports the findings of a shift towards a slower MHC phenotype. 4,44 The shift towards a slower, more aerobic-oxidative phenotype observed in SM, EDL, and SOL muscles from obese mice might also be related to the higher level of circulating glucocorticoids in ob/ob mice.…”

Section: Iiamentioning

confidence: 76%

“…4 Earlier work investigating respiratory muscles from genetically obese rodents supports the findings of a shift towards a slower MHC phenotype. 4,44 The shift towards a slower, more aerobic-oxidative phenotype observed in SM, EDL, and SOL muscles from obese mice might also be related to the higher level of circulating glucocorticoids in ob/ob mice. 5 Indeed, fibre type changes in the direction discussed above have been associated with elevated glucocorticoid concentrations.…”

Section: Iiamentioning

confidence: 76%

“…1 In an obese organism, skeletal muscle must fulfil its highly complex functions under conditions of increased body mass, 2 reduced activity, 3 and other physical (e.g. higher respiratory rate 4 ) and hormonal (e.g. elevated glucocorticoids 2,5 and adipokines 6 ) changes associated with obesity.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse

et al. 2009

View full text Add to dashboard Cite

Background: Knowledge of the morphological and biochemical alterations occurring in skeletal muscles of obese animals is relatively limited, particularly with respect to non-limb muscles and relationship to fibre type. Objective: Sternomastoid (SM; fast-twitch), extensor digitorum longus (EDL; fast-twitch), and soleus (SOL; mixed) muscles of ob/ob mouse (18-22 weeks) were examined with respect to size (mass, muscle mass-to-body mass ratio, cross-sectional area (CSA)), fibre CSA, protein content, myosin heavy chain (MHC) content, MHC isoform (MHC i ) composition, MHC i -based fibre type composition, and lactate dehydrogenase isoenzyme (LDH iso ) composition. Results: Compared with (control) muscles from lean mice, all the three muscles from ob/ob mice were smaller in size (by 13-30%), with SM and EDL being the most affected. The CSA of IIB and IIB þ IID fibres (the predominant fibre types in SM and EDL muscles) was markedly smaller (by B30%) in ob/ob mice, consistent with differences in muscle size. Total protein content (normalised to muscle mass) was significantly lower in EDL (À9.7%) and SOL (À14.1%) muscles of ob/ob mice, but there were no differences between SM, EDL, and SOL muscles from the two animal groups with respect to MHC content (also normalised to muscle mass). Electrophoretic analyses of MHC i composition in whole muscle homogenates and single muscle fibres showed a shift towards slower MHC i content, slower MHC i containing fibres, and a greater proportion of hybrid fibres in all the three muscles of ob/ob mice, with a shift towards a more aerobic-oxidative phenotype also observed with respect to LDH iso composition. Conclusion: This study showed that SM, EDL, and SOL muscles of ob/ob mice display size reductions to an extent that seems to be largely related to fibre type composition, and a shift in fibre type composition that may result from a process of structural remodelling, as suggested by the increased proportion of hybrid fibres in muscles of ob/ob mice.

show abstract

Section: Iiamentioning

confidence: 76%

Section: Iiamentioning

confidence: 76%

See 1 more Smart Citation

Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Defects in oxidative capacity alter cardiac function through decreased sarco (endo)plasmic reticulum Ca 2+ -ATPase (SERCA) isozyme 2a (SERCA2a) activity and the redistribution of myosin heavy chain (MHC) isozymes [16][17][18]. Alterations in MHC isozymes have been reported in obesity-related respiratory complications, which may be attenuated by leptin repletion [19,20]. Although leptin is considered an essential player in obesity and diabetes [4,11], the cellular mechanism(s) responsible for cardiac dysfunction in leptindeficient obesity have not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis: Obesity is an independent risk factor for heart diseases but the underlying mechanism is not clear. This study examined cardiac contraction, oxidative stress, oxidative modification of sarco(endo) plasmic reticulum Ca 2+ -ATPase (SERCA) and the myosin heavy chain (MHC) isoform switch in obese mice. Methods: Mechanical properties were evaluated in ventricular myocytes from C57BL/6J lean and Lep/Lep obese mice (formerly known as ob/ob mice), including peak shortening (PS), time to 50 or 90% PS, time to 50 or 90% relengthening (TR 50 , TR 90 ), maximal velocity of shortening/relengthening (±dL/dt), intracellular Ca 2+ and its decay (τ). Oxidative stress, lipid peroxidation, protein damage and SERCA activity were assessed by glutathione/glutathione disulfide, malondialdehyde, protein carbonyl and 45 Ca 2+ uptake, respectively. NADPH oxidase was determined by immunoblotting. Results: Myocytes from Lep/Lep mice displayed depressed PS and ± dL/dt, prolonged TR 50 , TR 90 , elevated resting [Ca 2+ ] i , prolonged τ, reduced contractile capacity at high stimulus frequencies and diminished responsiveness to extracellular Ca 2+ compared with lean controls. Cardiac glutathione/glutathione disulfide was decreased whereas malondialdehyde, protein carbonyl, membrane p47 phox and membrane gp91 phox were increased in the Lep/Lep group. SERCA isoenzyme 2a was markedly modified by oxidation in Lep/ Lep hearts and associated with decreased 45 Ca 2+ uptake. The MHC isozyme displayed a shift from the α to the β isoform in Lep/Lep hearts. Short-term incubation of angiotensin II with myocytes mimicked the mechanical defects, SERCA oxidation and 45 Ca 2+ uptake seen in Lep/ Lep myocytes. Incubation of the NADPH oxidase inhibitor apocynin with Lep/Lep myocytes alleviated contractile defects without reversing SERCA oxidation or activity. Conclusions/interpretation: These data indicate that obesity-related cardiac defects may be related to NADPH oxidase activation, oxidative damage to SERCA and the MHC isozyme switch.

show abstract

“…Recently, a number of authors have speculated that changes in serum leptin levels or leptin-receptor insensitivity may be involved in the pathogenesis of progressive obesity in patients with OSA [4]. Leptin has been found to reduce appetite and simultaneously to increase respiratory drive in an animal model [5,6]. In humans, the situation may be expected to be more complicated.…”

mentioning

confidence: 99%

Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment

Harsch¹,

Konturek²,

Koebnick³

et al. 2003

European Respiratory Journal

249

162

View full text Add to dashboard Cite

Serum leptin and ghrelin levels were investigated in patients with obstructive sleep apnoea (OSA) syndrome before and during continuous positive airways pressure (CPAP) treatment and compared with body mass index (BMI)-matched controls without OSA.Male patients (n=30) with OSA (apnoea/hypopnoea index=58 ¡ 16, BMI=32.6 ¡ 5.3 kg?m -2 ) underwent CPAP treatment. Fasting leptin and ghrelin were measured at baseline and 2 days, and in the case of leptin 2 months after initiation of treatment.Baseline plasma ghrelin levels were significantly higher in OSA patients than in controls. After 2 days of CPAP treatment, plasma ghrelin decreased in almost all OSA patients (n=9) to levels that were only slightly higher than those of controls (n=9). Leptin levels did not change significantly from baseline after 2 days of CPAP treatment, but were higher than in the control group. After 8 weeks, leptin levels decreased significantly, although the BMI of the patients showed no change. The decrease in leptin levels was more pronounced in patients with a BMI v30 kg?m -2 . These data indicate that the elevated leptin and ghrelin levels are not determined by obesity alone, since they rapidly decreased during continuous positive airways pressure therapy. Eur Respir J 2003; 22: 251-257 Obstructive sleep apnoea (OSA) is a common disorder affecting 2-4% of the adult population [1]. OSA is strongly associated with obesity. In a recent study involving 773 patients with OSA, only 6.5% had a normal body mass index (BMI), while 75.2% were obese (BMIo30 kg?m -2 ) [2]. Patients with OSA appear to be more likely to put on weight than equally obese subjects without OSA [3]. The mechanisms underlying this phenomenon remain obscure. Recently, a number of authors have speculated that changes in serum leptin levels or leptin-receptor insensitivity may be involved in the pathogenesis of progressive obesity in patients with OSA [4]. Leptin has been found to reduce appetite and simultaneously to increase respiratory drive in an animal model [5,6]. In humans, the situation may be expected to be more complicated. In recent studies, fasting leptin levels in patients with OSA decreased after initiation of continuous positive airways pressure (CPAP) treatment [7,8]. However, those leptin measurements were performed on awake individuals in the morning, when the respiratory situation was normalised, so that any linkage between leptin levels and respiratory effects is difficult in this setting. Furthermore, leptin levels are influenced by a multitude of factors, such as sex, body weight [9,10], the presence of hypertension, or specific medications impacting on leptin levels. Diurnal and ultradian variations in serum leptin levels are further factors complicating profound insights concerning significant respiratory effects [11][12][13].However, the finding that a hormone like leptin is able to cover a variety of biological functions, beyond its well-investigated role for the regulation of body weight and energy expenditure, also prompted the present aut...

show abstract

Leptin attenuates respiratory complications associated with the obese phenotype

Cited by 151 publications

References 37 publications

Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse

Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse

Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch

Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment

Contact Info

Product

Resources

About