Recombinant ob protein reduces feeding and body weight in the ob/ob mouse.

Abstract

To determine whether the product of the recently cloned ob gene functions as an adipose-related satiety factor, recombinant murine ob protein was administered intraperitoneally to ob/ob mice. Monomeric ob protein given as single morning injections to groups of three animals at seven doses ranging from 5 to 100 jpg reduced 24-h chow consumption in a dose-dependent manner from values of 81±6.8% of control (10-pmg dose, P = 0.04) to 29±7.7% of control (100-pug dose, P < 0.0001). Daily injections of 80 pzg of ob protein into six ob/ob mice for 2 wk led to an 11±1.6% decrease in body weight (P = 0.0009) and suppressed feeding to 26±4.9% of baseline (P < 0.0001), with significant reduction of serum insulin and glucose levels. The effect of recombinant ob protein on feeding was not augmented by cofactors secreted by adipose tissue, nor did exposure of adipose tissue to ob protein affect intracellular ob mRNA levels. Posttranslational modification of ob protein was not required for activity; however, addition of a hexahistidine tag to the amino terminus of the mature ob protein resulted in prolonged suppression of feeding after injection into ob/ob mice. These results demonstrate a direct effect of the ob protein to suppress feeding in the ob/ob mouse and suggest that this molecule plays a critical role in regulating total body fat content.(J. Clin.

Serotonin controlling feeding and satiety

“…Null-mutation of the Ob-gene causes severe obesity in mice (ob/ob mice) as does the mutation of the leptin receptor (db/db mice) [250,251]. Exogenous leptin reduces body weight in ob/ob-mice down to the level of wild-type control mice [252][253][254][255]. By contrast, leptin administration had no effect in db/db mice.…”

Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease

“…Furthermore, obesity has long been recognized to have detrimental effects on health including an increased risk of cardiovascular disease (CVD) [1]. In this regard, the recent cloning of the mouse (ob) and human (OB) obese genes and the characterization of its protein product, leptin [2], has been a breakthrough of potentially great importance for the understanding of the pathophysiology of obesity.Leptin has been shown to lower body weight by reducing food intake and increasing energy expenditure in leptin-deficient obese mice (ob/ob) and also to normalize blood glucose levels in the same animals [2][3][4][5][6][7][8]. Leptin is secreted by white adipose cells and is exclusively expressed in adipose tissue (AT) [2,[9][10][11][12][13].…”

Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse

“…Weight loss was associated levels. 12,[15][16][17][18] We therefore measured plasma glucose levwith 50 versus 30% reduction in food intake in Ad-leptinels following the various treatments of the ob/ob and and rh-leptin-treated groups, respectively. lean mice.…”

“…High blood glucose levels in ob/ob mice are reduced after leptin treatment. 12,[15][16][17][18] In this study, normalization of blood glucose levels in the ob/ob leptin-treated mice preceded the maximum weight loss, and occurred within the first few days after treatment. However, glucose levels were not affected in lean mice, despite the acute effect of leptin on both weight reduction and food intake, and regardless of whether delivery was by Ad-leptin transi- intake or body weight, and suggested a direct effect of leptin on metabolism.…”

“…1 these mice. 12,[15][16][17][18] Leptin exerts its appetite-suppressive function through Protein injection is frequently used to treat peptide horbinding to its receptor in the hypothalamus, where it is mone deficiencies. Although leptin can be delivered in suggested that leptin enters the brain by a transport systhis way, the treatment is compromised by its short durtem that can be saturated.…”