Leptin Rat
Description
Introduction to Leptin in Rats
Leptin, a 16-kDa hormone primarily secreted by adipose tissue, regulates energy balance, appetite, and metabolic processes in rats through interactions with leptin receptors (LEPR) . In rodent models, leptin serves as a critical feedback signal for adiposity, modulating food intake, energy expenditure, and thermogenesis . Research on "Leptin Rat" encompasses studies of leptin-deficient or leptin receptor knockout (KO) rats, which exhibit obesity, hyperphagia, and metabolic dysregulation, mimicking human obesity syndromes .
Leptin Receptor Knockout Rat Models
Homozygous leptin receptor knockout rats (Lepr −/−) display severe metabolic abnormalities:
These rats also develop dyslipidemia, hyperinsulinemia, and immune dysfunction, providing a model for studying obesity-related comorbidities .
Peripheral Leptin Infusion
-
Low-Dose Infusion (0.15–0.9 μg/day): Increased body fat by 13% in intact rats without altering food intake, suggesting leptin’s role in partitioning energy toward fat storage .
-
High-Dose Adenovirus-Induced Hyperleptinemia (8 ng/ml): Caused a 30–50% reduction in food intake and complete ablation of body fat in normal Wistar rats over 28 days .
Central Leptin Administration
-
3rd Ventricle Infusion: Reduced body fat in PBS-infused rats but increased food intake and adiposity when combined with hindbrain leptin receptor activation .
Cardiac Leptin System
-
Expression: Leptin and its receptors (OB-Ra, OB-Rb, OB-Re) are expressed in all cardiac regions, with higher levels in female rats .
-
Functional Role: Leptin modulates cardiac function via autocrine/paracrine signaling, influencing contractility and hypertrophy .
-
Ischemia Response: Global ischemia downregulated cardiac leptin and receptor expression, particularly in males .
Mechanisms of Leptin Resistance
-
Diet-Induced Resistance: Rats fed high-fat diets become unresponsive to leptin’s anorexigenic effects despite elevated circulating leptin levels .
-
Therapeutic Strategies: Combining leptin with sensitizers (e.g., amylin) may overcome resistance, as demonstrated in rodent studies .
Neonatal Leptin Exposure
Daily intraperitoneal leptin injections (0.3–1.0 μg/g) in neonatal rats reduced body weight gain by 10–15% over 10 days, independent of maternal milk intake .
Key Research Findings
Implications for Obesity Research
Leptin rat models elucidate mechanisms of energy balance, adipose tissue regulation, and metabolic disease. While leptin therapy alone is ineffective in obesity due to resistance, combinatorial approaches targeting leptin sensitization offer therapeutic potential . Cardiac leptin systems further highlight pleiotropic roles beyond energy homeostasis, including cardiovascular adaptation to stress .
Product Specs
(a) SEC-HPLC analysis.
(b) SDS-PAGE analysis.
1. UV spectroscopy at 280 nm, utilizing an absorbance value of 0.201 as the extinction coefficient for a 0.1% (1mg/ml) solution. This value is derived from the PC GENE computer analysis program of protein sequences (IntelliGenetics).
2. RP-HPLC analysis, employing a calibrated solution of Leptin rat as a reference standard.
Product Science Overview
Leptin was first identified as the protein product of the mouse obese (ob) gene. Mice with mutations in the obese gene that block the synthesis of leptin are found to be obese and diabetic, with reduced activity, metabolism, and body temperature . The discovery of leptin has significantly advanced our understanding of obesity and metabolic disorders.
Recombinant leptin refers to leptin that is produced through recombinant DNA technology. This involves inserting the gene that encodes leptin into a host organism, such as Escherichia coli (E. coli), to produce the hormone in large quantities. Recombinant rat leptin shares approximately 96% and 82% sequence identity with the mouse and human proteins, respectively .
The preparation of recombinant leptin typically involves the following steps:
- Gene Cloning: The gene encoding leptin is cloned into an expression vector.
- Transformation: The expression vector is introduced into a host organism, such as E. coli.
- Expression: The host organism is cultured under conditions that promote the expression of leptin.
- Purification: The leptin protein is purified from the host organism using techniques such as affinity chromatography.
Leptin regulates various physiological processes, including:
- Food Intake and Energy Expenditure: Leptin signals the brain to reduce appetite and increase energy expenditure.
- Insulin Sensitivity: Leptin enhances insulin sensitivity, which is crucial for glucose metabolism.
- Fertility: Leptin plays a role in reproductive function by regulating the hypothalamic-pituitary-gonadal axis.
- Immune System: Leptin has proinflammatory effects and regulates both innate and adaptive immune responses.
- Bone Metabolism: Leptin influences bone mass and density .
Recombinant rat leptin is widely used in research to study obesity, diabetes, and related metabolic disorders. It is also used to investigate the role of leptin in various physiological processes and disease states. For example, leptin knockout rats, which lack the leptin gene, are used as models to study the effects of leptin deficiency .
