Serum Leptin Concentration is Associated with Incident Frailty in Older Adults

Abstract

Obesity has been associated with higher risk of frailty in older adults, but the pathophysiological mechanisms are unclear. No previous study has examined the association between leptin, an adipokine, and the risk of frailty in older adults, and whether this association could be explained by insulin resistance or chronic inflammation. Data were taken from 1,573 individuals without diabetes mellitus, aged ≥60 years, from the Seniors-ENRICA cohort. In 2008-2010, leptin, the homeostasis model assessment of insulin resistance (HOMA-IR) and C-reactive protein (CRP) were measured. Study participants were followed-up through 2012 to assess incident frailty, defined as at least two of the following Fried criteria: exhaustion, weakness, low physical activity, and slow walking speed. Analyses were performed with logistic regression and adjusted for the main confounders. Over a median follow-up of 3.5 years, 280 cases of incident frailty were identified. Compared to individuals in the lowest tertile of serum leptin, those in the highest tertile showed an increased risk of frailty (odds ratio [OR]: 2.12; 95% confidence interval [CI]: 1.47-3.06; p-trend <0.001). Further adjustment for the percentage of body fat led to an OR of 1.69 (95% CI: 1.11-2.61; p-trend=0.01). After additional adjustment for HOMA-IR and CRP, the OR for frailty was 1.59 (95% CI: 1.01-2.52; p-trend=0.04). Results did not vary according to sex, abdominal obesity or the percentage of body fat. Being in the highest versus lowest tertile of leptin was associated with increased risk of exhaustion (OR: 2.16; 95% CI: 1.32-3.55; p-trend=0.001) and muscle weakness (OR: 1.77; 95% CI: 1.25-2.51; p-trend=0.001), in the analyses adjusted for potential confounders and body fat. Higher leptin concentration was associated with greater risk of frailty in older adults. This association was only modestly explained by insulin resistance and chronic inflammation, as measured by CRP.

Expression of adipocytokine genes and their content in various adipose tissue sites in patients with heart diseases

“…Leptin receptors gene expression in cell cultures may depend on leptin concentration. It was shown that the addition of exogenous leptin to the cell culture reduced the expression of its receptors, while the decrease in the concentration of circulating leptin during prolonged fasting was accompanied by an increase in receptor mRNA levels [36,37]. In addition, it is currently hypothesized that increased concentrations of the leptin R inhibit leptin effects, while reduced concentrations of the leptin receptor re ect low membrane expression of the receptor.…”

The conundrum of patients with obesity, exercise intolerance, elevated ventricular filling pressures and a measured ejection fraction in the normal range

“…Leptin's effect to augment renal sodium reabsorption occurs by a direct tubular action, by enhancing the synthesis of aldosterone and by mediating the high renal sympathetic nerve traffic that is seen in obesity . High levels of leptin are strongly associated with co‐morbidities, and leptin participates in the inflammatory response in rheumatoid arthritis, psoriasis and Crohn's disease . Increases in leptin are associated with ventricular fibrosis and diastolic filling abnormalities, and contribute to the atrial fibrosis that leads to arrhythmias .…”

Leptin resistance: unsolved diagnostic issues

“…Экспрессия рецепторов лептина в клеточных культурах может быть связана с концентрацией лептина. Добавление экзогенного лептина к культуре клеток снижало экспрессию его рецепторов [44], тогда как снижение концентрации циркулирующего лептина при длительном голодании, напротив, сопровождается ростом уровня мРНК OB-R [45].…”