Impaired leptin signal transduction with age-related obesity

Scarpace, Philip J.; Matheny, Michael; Shek, Eugene W.

doi:10.1016/s0028-3908(00)00014-9

Cited by 96 publications

(61 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This, together with the fact that body weight and daily food intake are also higher in old than in young rats [7], suggest that old Wistar rats present leptin resistance. This agrees well with the data of other authors who described leptin resistance in other rodent models of ageing [12,13,18,23]. A decrease in the ratio CSF-to-serum leptin concentrations suggested that a failure at the level of the transport from blood to CSF could be the cause of leptin resistance in obese humans [8].…”

Section: Discussionsupporting

confidence: 92%

“…leptin administration with similar sensitivity as lean mice but did not respond to peripheral leptin administration. In old obese Fisher 344XBN rats, leptin resistance has been reported to occur at the central level [13,24] and to involve alterations in leptin signal transduction cascade [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…Alteration of leptin transport across the blood-brain barrier has been proposed to occur in obese humans [8,9], in New Zealand obese mice [10] and in diet-induced obese mice [11]. An impairment in the leptin signal transduction cascade has been shown in the old Fisher 344XBN rat [12,13].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats

et al. 2002

View full text Add to dashboard Cite

Aims/hypothesis. Ageing is associated with insulin and leptin resistance in mammals. These alterations might be caused by the increased adiposity associated with ageing, by ageing alone or both. We studied whether leptin resistance occurs at the central level in the Wistar rat and we aimed to discriminate between the effects of ageing from those of the increased adiposity associated with ageing. Methods. Leptin was infused intracerebroventricularly at a constant rate in young adult, old and old Wistar rats fasted for 3 months, using osmotic pumps. The effects on body weight, daily food intake, Lee index, adiposity and serum leptin values were analysed. The effect of food restriction on the expression of the long form of leptin receptor in the hypothalamus was also studied. Results. Leptin decreased daily food intake and body weight in young and old Wistar rats. With a dose of 10 µg/day similar responses were obtained in young and old rats but with a dose of 0.2 µg/day, only young rats showed decreases in these parameters. Foodrestriction in old rats lowered adiposity and serum leptin to values close to those of young rats, recovered responsiveness to i.c.v. administration of leptin at the dose of 0.2 µg/day and increased leptin receptor expression in the hypothalamus. Conclusion/interpretation. Our data show that old Wistar rats have a decreased response to leptin at the central level. Food-restriction recovers leptin responsiveness and increases leptin receptor in the hypothalamus suggesting that adiposity plays a key role in the development of leptin resistance associated with ageing. [Diabetologia (2002[Diabetologia ( ) 45:997-1003 Keywords Leptin, leptin-resistance, food-restriction, ageing, Wistar rat.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats

et al. 2002

View full text Add to dashboard Cite

show abstract

“…As mentioned, studies on rodents demonstrated that aged individuals show reduced responsiveness to externally derived leptin (Scarpace et al 2000a;Scarpace et al 2000b). Thus, it has been proposed that leptin signaling might be impaired due to an age-related elevation in obesity and serum leptin levels (Scarpace and Tumer 2001;Petervari et al 2014;Scarpace et al 2000b). Maintaining stable AT mass and its function seems to be crucial for physiological homeostasis during the ageing process, which may involve regular leptin signaling (Carter et al 2013).…”

Section: Leptinmentioning

confidence: 92%

“…Myers et al (2012) concluded that increased leptin levels in obese subjects might be functionally relevant, since even extremely obese individuals demonstrate beneficial changes in satiety and energy expenditure upon weight loss Wing et al 1996), although these changes are inhibited by exogenous leptin administration (Myers et al 2012). As mentioned, studies on rodents demonstrated that aged individuals show reduced responsiveness to externally derived leptin (Scarpace et al 2000a;Scarpace et al 2000b). Thus, it has been proposed that leptin signaling might be impaired due to an age-related elevation in obesity and serum leptin levels (Scarpace and Tumer 2001;Petervari et al 2014;Scarpace et al 2000b).…”

Section: Leptinmentioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

300

175

View full text Add to dashboard Cite

Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

show abstract

Disruption of leptin signalling in a mouse model of Alzheimer’s disease

et al. 2018

View full text Add to dashboard Cite

Disruption of leptin signalling has been implicated as playing a role in the development of Alzheimer's disease (AD). Leptin has previously been shown to be affected by amyloid-beta (Aβ)-related signalling; however, pathways that link leptin to the disease pathogenesis have not been determined. To characterize the association between increasing age-dependent Aβ levels with leptin signalling and the vulnerable brain regions in AD, we assessed the mRNA and protein expression profile of leptin and leptin receptor (Ob-Rb) at 9 and 18-month-age in APP/PS1 mice. Immunohistochemical labelling demonstrated that leptin and Ob-Rb proteins were localised to neocortical and hippocampal neurons in APP/PS1 and wildtype (WT) mice. Neuronal leptin and Ob-Rb immunolabelling was more prominent in the neocortex of both groups at 9 month of age, while, at 18 months, labelling was reduced in the hippocampus of APP/PS1 mice relative to WT. Immunoblotting analysis demonstrated decreased hippocampal leptin levels, concomitantly with an increased Ob-Rb levels, in APP/PS1 mice compared with WT controls at 18 month of age. While no leptin mRNA was found in either of the groups analysed, Ob-Rb mRNA was significantly decreased in the hippocampus of APP/PS1 mice at both ages analysed. In addition, a significant decreased protein kinase B (Akt) activity concomitantly with an upregulation of suppressor of cytokine signaling-3 (SOCS3) and protein-tyrosine phosphatase 1B (PTP1B) transcripts was present. Thus, these results collectively indicate alterations of leptin signalling in the hippocampus of APP/PS1 mice, providing novel insights about the pathways that could link aberrant leptin signaling to the pathological changes of AD.

show abstract

Impaired leptin signal transduction with age-related obesity

Cited by 96 publications

References 23 publications

Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats

Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats

Obesity and related consequences to ageing

Disruption of leptin signalling in a mouse model of Alzheimer’s disease

Contact Info

Product

Resources

About