Evaluation of new leptin fragments on food intake and body weight of normal rats.
ABSTRACT Leptin, a protein hormone originating from adipose tissue, circulates in the plasma and affects the energy balance by interacting with the hypothalamus. Leptin plays an important role in the regulation of a variety of physiological functions, including food intake, body temperature and body weight maintenance. Tertiary structure of the leptin molecule reveals the existence of a four-helix bundle that is characteristic of the short-helix cytokines. To identify regions of the leptin molecule responsible for its bioactivity, we have recently synthesized six peptides based on the protein three-dimensional structure. Our results indicated that the fragments Ac-hLEP(92-115)-NH(2) (IV) and Ac-[Ser(117)]-hLEP(116-140)-NH(2) (V) were recognized by leptin receptor present in hp-75 cells validating that this region of the molecule contain the functional epitope of the leptin molecule. In the present study, a new series of decapeptides encompassing the region of fragments IV and V of leptin were synthesized, and their effects on body weight and food intake were assessed when administered into the lateral cerbroventricle of normal rats. Peptides were synthesized by SPPS, purified by RP-HPLC and characterized by LC/ESI-MS. We also performed a conformational study of the peptides by circular dichroism in order to correlate the biological activity and secondary structure of the leptin fragments. Among the fragments tested, we found that Ac-hLEP(110-119)-NH(2) (VI) induce a significant reduction in both body weight and food intake. The use of synthetic leptin-derivate fragments may offer the basis for the development of compounds with potential application in human obesity or to its related metabolic dysfunctions.
- SourceAvailable from: Gustavo D Pimentel[show abstract] [hide abstract]
ABSTRACT: This review reports the evidence for a relation between long-term coffee intake and risk of type 2 diabetes mellitus. Numerous epidemiological studies have evaluated this association and, at this moment, at least fourteen out of eighteen cohort studies revealed a substantially lower risk of type 2 diabetes mellitus with frequent coffee intake. Moderate coffee intake (>/=4 cups of coffee/d of 150 mL or >/=400 mg of caffeine/d) has generally been associated with a decrease in the risk of type 2 diabetes mellitus. Besides, results of most studies suggest a dose-response relation, with greater reductions in type 2 diabetes mellitus risk with higher levels of coffee consumption. Several mechanisms underlying this protective effect, as well as the coffee components responsible for this association are suggested. Despite positive findings, it is still premature to recommend an increase in coffee consumption as a public health strategy to prevent type 2 diabetes mellitus. More population-based surveys are necessary to clarify the long-term effects of decaffeinated and caffeinated coffee intake on the risk of type 2 diabetes mellitus.Diabetology and Metabolic Syndrome 01/2009; 1(1):6. · 1.92 Impact Factor