Central Administration of Leptin Inhibits Food Intake and Activates the Sympathetic Nervous System in Rhesus Macaques1

Department of Nutrition, University of California, Davis, Davis, California, United States
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 03/1999; 84(2):711-7. DOI: 10.1210/jcem.84.2.5458
Source: PubMed

ABSTRACT The present study was performed to determine the effects of central administration of leptin on food intake and sympathetic nervous system activity in a nonrodent species, the rhesus monkey. Peripheral administration of leptin at doses (1 and 3 microg/kg, s.c.) that produced increments of circulating leptin concentrations within a physiological range did not inhibit food intake over the subsequent 3 days. In contrast, leptin (1 microg/kg, intracerebroventricularly) had no acute effect on food intake, but caused a significant and sustained suppression (40-50%) of food intake during the entire following day (P < 0.01). In addition, circulating norepinephrine levels increased by 55 +/- 16% (P < 0.02) 1 h after intracerebroventricular leptin administration, but did not increase after artificial cerebrospinal fluid administration. These results indicate that leptin can provide a signal to the central nervous system that decreases food intake in primates and in addition acutely activates the sympathetic nervous system. However, the results showing an acute increase in circulating leptin concentrations after peripheral administration of human leptin suggest that in primates, increases in circulating leptin within the physiological range do not acutely regulate food intake. Leptin may be more important in regulating food intake when there are sustained changes in circulating concentrations of leptin (e.g. with obesity, prolonged energy restriction, or diabetes).

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    • "No significant correlations were found between serum adiponectin and LF HRV or HF HRV in another group of patients with Type 2 diabetes (Wakabayashi and Aso, 2004). Leptin, which is elevated in most obese individuals, stimulates the sympathetic nervous system and increases sympathetic nerve activity to several organs and glands (Eikelis et al., 2003; Haynes, 2000; Mark, 2013; Tang-Christensen et al., 1999). Moreover, the effect of leptin on sympathetic nerve activity is dosedependent , ranging from 228% 6 63% to 388% 6 171% at 1,000 mg/kg in one study (Haynes et al., 1997). "
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    ABSTRACT: Objectives Police officers have a high prevalence of cardiovascular disease (CVD). Reduced heart rate variability (HRV) is known to increase CVD risk. Leptin and adiponectin may be related to CVD health. Therefore, our objective was to investigate the relationship between these variables and HRV.Methods Leptin and adiponectin levels were measured in 388 officers from the Buffalo Cardio-Metabolic Occupational Police Stress study. HRV was assessed according to methods published by the Task Force of the European Society of Cardiology and the North American Society of Pacing Electrophysiology for measurement and analysis of HRV. Mean values of high-frequency (HF) and low-frequency (LF) HRV were compared across tertiles of leptin and adiponectin using analysis of variance and analysis of covariance; trends were assessed using linear regression models.ResultsLeptin, but not adiponectin, was significantly and inversely associated with HRV. Body mass index (BMI) and percent body fat significantly modified the association between leptin and LF (but not HF) HRV. Among officers with BMI < 25 kg/m2, leptin was not significantly associated with HRV. However, among officers with BMI ≥ 25 kg/m2, leptin was inversely associated with HRV, after adjustment for age, gender, and race/ethnicity; HF HRV, P = 0.019 and LF HRV, P < 0.0001. Similarly, among officers with percent body fat ≥ 25.5%, leptin and LF HRV showed significant, inverse associations (adjusted P = 0.001).Conclusions Leptin levels were inversely associated with LF HRV, especially among officers with increased adiposity. Increased leptin levels may be associated with CVD-related health problems. Am. J. Hum. Biol. 27:184-191, 2015. © 2014 Wiley Periodicals, Inc.
    American Journal of Human Biology 06/2014; 71 Suppl 1(2):A65-6. DOI:10.1136/oemed-2014-102362.204 · 1.70 Impact Factor
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    • "Leptin may act primarily in signaling starvation rather than mediating satiety (21;22). However leptin administration has been shown to decrease food intake in animals (23) and humans (24). However, it is not clear whether leptin could explain the negative association of FMI with food intake when accounting for FFMI. "
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    ABSTRACT: Background Obesity is the result of chronic positive energy balance. The mechanisms underlying the regulation of energy homeostasis and food intake are not understood. Despite large increases in fat mass (FM), recent evidence indicates that fat-free mass (FFM) rather than FM is positively associated with intake in humans. Methods In 184 humans (73F/111M; age 34.5±8.8y; % body fat [PFAT] 31.6±8.1%) we investigated the relationship of FFM index (FFMI kg*m2), FM index (FMI kg*m2;), and 24-hour energy expenditure (EE, n=127) with ad-libitum food intake using a 3d vending machine paradigm. Mean daily calories (CAL), and macronutrient intake (PRO, CHO, FAT) were determined and used to calculate the relative caloric contribution of each (%PRO, %CHO, %FAT) and percent of caloric intake over weight maintaining energy needs (%WMEN). Results FFMI was positively associated with CAL (p<0.0001), PRO (p=0.0001), CHO (p=0.0075), and FAT (p<0.0001). This remained significant after adjusting for FMI. Total EE predicted CAL and macronutrient intake (all p<0.0001). FMI was positively associated with CAL (p=0.019), PRO (p=0.025) and FAT (p=0.0008). In models with both FFMI and FMI, FMI was negatively associated with CAL (p=0.019) and PRO (p=0.033). Both FFMI and FMI were negatively associated with %CHO and positively associated with %FAT (all p<0.001). EE and FFMI (adjusted for FMI) were positively (EE p=0.0085; FFMI p=0.0018) and FMI negatively (p=0.0018; adjusted for FFMI) associated with %WMEN. Conclusion Food and macronutrient intake is predicted by FFMI and to a lesser degree by FMI. FFM and FM may have opposing effects on energy homeostasis.
    International journal of obesity (2005) 05/2013; 38(2). DOI:10.1038/ijo.2013.85 · 5.00 Impact Factor
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    • "Since LepRb neurons are abundant in these brain regions (Leshan et al., 2006; Scott et al., 2009), it is likely that coordinated leptin signaling in multiple brain regions is required for proper regulation of hepatic lipid content. Leptin is known to activate the sympathetic nervous system in rodents, primates and humans through increased catecholamine output (Buettner et al., 2008; Rosenbaum et al., 2005; Satoh et al., 1999; Tang-Christensen et al., 1999). We shows that chronic central leptin infusion, via PI3K, elevates liver sympathetic activity and that NE directly exerts an effect on liver lipogenic gene expression. "
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    ABSTRACT: Hepatic steatosis is generally thought to develop via peripheral mechanisms associated with obesity. We show that chronic central infusion of leptin suppresses hepatic lipogenic gene expression and reduces triglyceride content via stimulation of hepatic sympathetic activity. This leptin function is independent of feeding and body weight but requires phosphatidylinositol 3-kinase (PI3K) signaling. Attenuation of leptin-induced PI3K signaling, brought about by transgenic expression of phosphatase and tensin homolog (PTEN) in leptin receptor neurons, leads to decreased hepatic sympathetic tone and increased triglyceride levels without affecting adiposity or hepatic insulin signaling. Central leptin's effects on hepatic norepinephrine levels and triglyceride content are blunted in these mutant mice. Simultaneous downregulation of PI3K and signal transducer and activator of transcription-3 (Stat3) in leptin receptor neurons does not exacerbate obesity but causes more severe hepatic steatosis. Together, our results indicate that central cellular leptin resistance in PI3K signaling manifests as hepatic steatosis without causing obesity.
    Cell metabolism 12/2011; 14(6):791-803. DOI:10.1016/j.cmet.2011.11.001 · 17.57 Impact Factor
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