Role of leptin resistance in the development of obesity in older patients.

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Role of leptin resistance in the development of obesity in older patients.

Author(s): Sophie Carter, Alexandre Caron, Denis Richard, Frédéric Picard

Publication date: 2013

Journal: Clinical Interventions in Aging

Keywords: aging, brown adipose tissue, insulin sensitivity, leptin, obesity

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Abstract

Obesity is a global epidemic associated with aging-like cellular processes; in both aging and obesity, resistance to hormones such as insulin and leptin can be observed. Leptin is a circulating hormone/cytokine with central and peripheral effects that is released mainly by subcutaneous white adipose tissue. Centrally, leptin controls food intake, energy expenditure, and fat distribution, whereas it controls (among several others) insulin sensitivity, free fatty acids (FFAs) oxidation, and lipolysis in the periphery. Aging is associated with important changes in both the distribution and the composition of adipose tissue. Fat is redistributed from the subcutaneous to the visceral depot and increased inflammation participates in adipocyte dysfunction. This redistribution of adipose tissue in favor of visceral fat influences negatively both longevity and healthy aging as shown in numerous animal models. These modifications observed during aging are also associated with leptin resistance. This resistance blunts normal central and peripheral functions of leptin, which leads to a decrease in neuroendocrine function and insulin sensitivity, an imbalance in energy regulation, and disturbances in lipid metabolism. Here, we review how age-related leptin resistance triggers metabolic disturbances and affects the longevity of obese patients. Furthermore, we discuss the potential impacts of leptin resistance on the decline of brown adipose tissue thermogenesis observed in elderly individuals.

Most cited references 169

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Ali Mokdad, Earl S. Ford, Barbara BOWMAN … (2003)

Obesity and diabetes are increasing in the United States. To estimate the prevalence of obesity and diabetes among US adults in 2001. Random-digit telephone survey of 195 005 adults aged 18 years or older residing in all states participating in the Behavioral Risk Factor Surveillance System in 2001. Body mass index, based on self-reported weight and height and self-reported diabetes. In 2001 the prevalence of obesity (BMI > or =30) was 20.9% vs 19.8% in 2000, an increase of 5.6%. The prevalence of diabetes increased to 7.9% vs 7.3% in 2000, an increase of 8.2%. The prevalence of BMI of 40 or higher in 2001 was 2.3%. Overweight and obesity were significantly associated with diabetes, high blood pressure, high cholesterol, asthma, arthritis, and poor health status. Compared with adults with normal weight, adults with a BMI of 40 or higher had an odds ratio (OR) of 7.37 (95% confidence interval [CI], 6.39-8.50) for diagnosed diabetes, 6.38 (95% CI, 5.67-7.17) for high blood pressure, 1.88 (95% CI,1.67-2.13) for high cholesterol levels, 2.72 (95% CI, 2.38-3.12) for asthma, 4.41 (95% CI, 3.91-4.97) for arthritis, and 4.19 (95% CI, 3.68-4.76) for fair or poor health. Increases in obesity and diabetes among US adults continue in both sexes, all ages, all races, all educational levels, and all smoking levels. Obesity is strongly associated with several major health risk factors.

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Age-related changes in total and regional fat distribution.

Jennifer L. Kuk, Travis Saunders, Lance E. Davidson … (2009)

Aging is associated with progressive changes in total and regional fat distribution that have negative health consequences. Indeed, a preferential increase in abdominal fat, in particular visceral fat, combined with a decrease in lower body subcutaneous fat are commonly cited in the literature. These age-related changes in body composition can occur independent of changes in total adiposity, body weight or waist circumference, and represent a phenotype closely associated with increased morbidity and mortality risk. Tissues such as the heart, liver and skeletal muscle in the elderly have increased fat deposition, which increases risk for insulin resistance and cardiovascular disease. Furthermore, aging is associated with increased fat content within bone marrow, which exposes the elderly to fracture risk beyond that associated with low bone mineral density alone. Many of the age-associated body compositional changes cannot be detected by simple anthropometric measures alone, and the influence of gender, race or ethnicity, and physical activity patterns on these changes is unclear. This review will explore some of these age-related changes in total and regional fat distribution. Consideration will also be given to the strengths and limitations associated with some of the anthropometric methodologies employed for assessing these changes.

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Mechanisms of disease: is osteoporosis the obesity of bone?

Clifford Rosen, Mary Bouxsein (2006)

Osteoporosis and obesity, two disorders of body composition, are growing in prevalence. Interestingly, these diseases share several features including a genetic predisposition and a common progenitor cell. With aging, the composition of bone marrow shifts to favor the presence of adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. Secondary causes of osteoporosis, including diabetes mellitus, glucocorticoids and immobility, are associated with bone-marrow adiposity. In this review, we ask a provocative question: does fat infiltration in the bone marrow cause low bone mass or is it a result of bone loss? Unraveling the interface between bone and fat at a molecular and cellular level is likely to lead to a better understanding of several diseases, and to the development of drugs for both osteoporosis and obesity.