Leptin in Sarcopenic Visceral Obesity: Possible Link between Adipocytes and Myocytes

et al. (2011) Leptin in Sarcopenic Visceral Obesity: Possible Link between Adipocytes and Myocytes. PLoS ONE 6(9): e24633. doi:10.1371/journal.pone.0024633 Leptin in Sarcopenic Visceral Obesity: Possible Link between Adipocytes and Myocytes Katsuhiko Kohara 0 Masayuki Ochi 0 Yasuharu Tabara 0 Tokihisa Nagai 0 Michiya Igase 0 Tetsuro 0 Gian Paolo Fadini, University of Padova, Medical School, Italy 0 1 Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan, 2 Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Ehime, Japan, 3 Proteo-Medicine Research Center, Ehime University Graduate School of Medicine , Ehime , Japan The combination of sarcopenia, age-related loss of muscle strength and mass, and obesity has been recognized as a new category of obesity among the elderly. Given that leptin has been hypothesized to be involved in the pathogenesis of sarcopenic obesity, we investigated the relationship between plasma leptin levels and thigh muscle sarcopenia and visceral obesity. Thigh muscle cross-sectional area (CSA) and visceral fat area were measured using computed tomography as indices for muscle mass and visceral fat, respectively, in 782 middle-aged to elderly subjects (303 men and 479 women), participating in a medical check-up program. Visceral obesity was defined as visceral fat area .100 cm2, and sarcopenia was defined as , (one standard deviation 2 mean of thigh muscle CSA/body weight of young subjects [aged ,50 years]). Thigh muscle CSA was significantly and negatively associated with plasma levels of leptin in both men (b = -0.28, p,0.0001) and women (b = -0.20, p,0.0001), even after correcting for other confounding parameters, including age, body weight, body height, visceral fat area, blood pressure, homeostatic model assessment index, and high sensitive C reactive protein. Subjects were divided into four groups based on presence or absence of sarcopenia or visceral obesity. Plasma levels of leptin were higher in subjects with sarcopenic visceral obesity than in those with either sarcopenia or visceral obesity alone. These findings indicate that sarcopenic visceral obesity is a more advanced, and suggest that leptin may link visceral obesity and sarcopenia. - Competing Interests: The authors have declared that no competing interests exist. Obesity, particularly visceral obesity, is a global pandemic known to be related to numerous pathological conditions, including metabolic syndrome, diabetes, hypertension, and cardiovascular disease [13]. Sarcopenia, which is the age-related loss of muscle mass, is another concern in todays aging society [4]. In particular, sarcopenia in the legs leads to functional impairments such as postural instability, falling, and frailty, eventually culminating in loss of independence and death [5]. Recent studies have turned attention to sarcopenic-obesity, a deadly combination of the above two conditions which synergistically deteriorates metabolic disorders as well as functional abnormalities [13]. Prevalence of sarcopenic-obesity is increasing in industrialized countries due to increased prevalence of obesity itself and sarcopenia in obese subjects [13,6]. Determining the underlying mechanisms linking sarcopenia and obesity is therefore crucial to enacting effective intervention protocols. Adipocyte-myocyte crosstalk via adipokines is believed to underlie the pathophysiology of obesity-related disorders [7]. Leptin is released from adipocytes and exerts a range of pathological and physiological actions on a number of organs, including skeletal muscle [8]. Specifically, leptin acts on skeletal muscles to stimulate lipolysis and insulin sensitivity [9]. Serum levels of leptin increase with fat accumulation [810]. Although its central effect decreases in this state, leptin maintains its peripheral effect, subsequently leading to stimulation of the sympathetic nervous system and platelet aggregation, effects which may underlie the connection between obesity and cardiovascular diseases such as hypertension [11] and atherosclerosis [10]. Leptin receptors have been shown to be down-regulated by leptin itself or via insulin resistance [10]. Since skeletal muscle is the major site of glucose consumption, presence of sarcopenia is another risk factor in developing insulin resistance [13]. Further, leptin receptor numbers may be reduced along with muscle mass in patients with sarcopenia, possibly resulting in further increases in plasma leptin concentration. These findings suggest that leptin may play a greater role in sarcopenic obesity than in simple obesity. However, studies evaluating the relationship between sarcopenia and circulating leptin levels have thus far drawn inconclusive results due to a small patient population [1214]. Here, we conducted a cross-sectional study to investigate relationships between plasma leptin levels and sarcopenia and obesity in 782 middle-aged to elderly subjects participating in a medical check-up program in Japan. Study subjects Subjects were independent middle-aged to elderly persons recruited from among consecutive visitors to the Anti-Aging Center at Ehime University Hospital from March 2006 to March 2009. They attended the voluntary medical check-up program, Anti-Aging Doc, a program provided to general residents of Ehime Prefecture, Japan, specifically designed to evaluate agingrelated disorders, including atherosclerosis, cardiovascular disease, physical function, and mild cognitive impairment [15,16]. Of the 844 consecutive patients initially approached, a total of 782 who agreed with the study aims and protocols, gave written consent to all procedures, and were free of any history of symptomatic cardiovascular events including peripheral arterial diseases, stroke, coronary heart disease, and congestive heart failure were analyzed. All participants were physically independent in their daily lives. The series of studies to which the present study belongs was approved by the Ethics Committee of Ehime University Graduate School of Medicine. Measurement of femoral muscle cross-sectional area and visceral fat area Femoral muscle cross-sectional area (CSA) was measured using computed tomography (CT; LightSpeed VCT; GE Healthcare, Tokyo, Japan) at the mid-thigh, measured as the midpoint from the inguinal crease to the proximal pole of the patella [16]. The muscle CSA (cm2) was computed using an attenuation range of 0 to 100 Hounsfield units. Visceral fat area was measured using CT at the level of the umbilicus, with attenuation ranging from 150 to 50 Hounsfield units. CT images were obtained with a minimal slice width of 5 mm and analyzed using OsiriX software (OsiriX Foundation, Geneva, Switzerland) (Fig. 1) [17]. All images were analyzed by a single investigator under blinded conditions (O.M.). Figure 1. Thigh muscle CT (top) at the mid-thigh level and abdominal CT (bottom) at umbilicus level. Thig (...truncated)