Leptin in chronic kidney disease: a link between hematopoiesis, bone metabolism, and nutrition

Abstract

Anemia, dyslipidemia, malnutrition, together with mineral and bone disorders are common complications in patients with chronic kidney disease (CKD). All are associated with increased risk of mortality. Leptin is a small peptide hormone that is mainly but not exclusively produced in adipose tissue. It is also secreted by normal human osteoblasts, subchondral osteoblasts, placental syncytiotrophoblasts, and the gastric epithelium. Leptin binds to its receptors in the hypothalamus to regulate bone metabolism and food intake. Leptin also has several other important metabolic effects on peripheral tissues, including the liver, skeletal muscle, and bone marrow. Leptin is cleared principally by the kidney. Not surprisingly, serum leptin appears to increase concurrently with declines in the glomerular filtration rate in patients with CKD. A growing body of evidence suggests that leptin might be closely related to hematopoiesis, nutrition, and bone metabolism in CKD patients. Results are conflicting regarding leptin in patients with CKD, in whom both beneficial and detrimental effects on uremia outcome are found. This review elucidates the discovery of leptin and its receptors, changes in serum or plasma leptin levels, the functions of leptin, relationships between leptin and the complications mentioned above, and pharmaceutical interventions in serum leptin levels in patients with CKD.

Hematological complications in anorexia nervosa

“…Recently, Zhang and Wang 28 reported an increase in the preadipocyte factor Pref-1, a member of the epidermal growth factor-like family of proteins and regulator of adipocyte and osteoblast differentiation in patients with AN. 28 The consequence of this altered Pref-1 production was a defective generation of osteoblasts in the bone marrow.…”

“…28 The consequence of this altered Pref-1 production was a defective generation of osteoblasts in the bone marrow. As osteoblasts are strictly related with hematopoiesis, 26 it is possible to speculate that a reduction in their generation, following Pref-1 increased secretion, could interfere with hematopoiesis in AN subjects.…”

“…Furthermore, leptin was suggested to be involved in the development of the hematopoietic bone marrow through erythropoietic-stimulating agents. 27, 28 The imbalance of leptin/Pref-1 ratio could result in another perturbation of the microenvironment with consequent interference with hematopoiesis in patients with AN. However, this hypothesis will require further evaluation.…”

Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy

“…Its physiological roles include signaling long-term caloric intake and fat stores to the hypothalamus, thereby modifying food consumption and energy expenditure 18 . In CKD patients, leptin plays an important role in hematopoiesis, nutrition and bone metabolism 26 . SHPT, a familiar clinical manifestation of CKD with high mortality, is used to describe a broader clinical syndrome, including mineral, bone and calcific cardiovascular abnormalities 15 .…”

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

“…Leptin acts on the hypothalamic melanocortinergic system to decrease food intake and to increase energy expenditure by stimulating POMC neuronal activity while at the same time silencing neurons that express NPY and AgRP (Schwartz et al, 2000). Beyond its ability to decrease body weight, leptin exerts a remarkable variety of metabolic effects that, among many others, include the regulation of glucose metabolism (Pelleymounter et al, 1995;Hedbacker et al, 2010), stress and anxiety (Haleem, 2014), reproduction (Hebebrand et al, 2007;Müller et al, 2009), inflammation, and hematopoiesis (Fantuzzi and Faggioni, 2000;Zhang and Wang, 2014).…”