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The PI3K-Akt-FoxO1 pathway contributes to the actions of insulin and leptin in several cell types, including neurons in the CNS. However, identifying these actions in chemically identified neurons has proven difficult. To address this problem, we have developed a reporter mouse for monitoring PI3K-Akt signaling in specific populations of neurons, based on(More)
Circulating leptin and insulin convey information regarding energy stores to the central nervous system, particularly the hypothalamus. Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors. However, the physiological significance of concomitant leptin and insulin action on(More)
Mice lacking 5-HT 2C receptors (5-HT(2C)Rs) displayed hepatic insulin resistance, a phenotype normalized by re-expression of 5-HT(2C)Rs only in pro-opiomelanocortin (POMC) neurons. 5-HT(2C)R deficiency also abolished the anti-diabetic effects of meta-chlorophenylpiperazine (a 5-HT(2C)R agonist); these effects were restored when 5-HT(2C)Rs were re-expressed(More)
Studies have suggested that manipulations of the central melanocortin circuitry by pharmacological agents produce robust effects on the regulation of body weight and glucose homeostasis. In this review, we discuss recent findings from genetic mouse models that have further established the physiological relevance of this circuitry in the context of glucose(More)
Phosphatidyl inositol 3-kinase (PI3K) signaling in the hypothalamus has been implicated in the regulation of energy homeostasis, but the critical brain sites where this intracellular signal integrates various metabolic cues to regulate food intake and energy expenditure are unknown. Here, we show that mice with reduced PI3K activity in the ventromedial(More)
BACKGROUND AND PURPOSE Most forms of human obesity are characterized by impaired leptin sensitivity and, therefore, the effectiveness of anti-obesity leptin therapy in these leptin-resistant obese patients is marginal. Hence, the development of strategies to increase leptin sensitivity is of high priority in the field of obesity research. EXPERIMENTAL(More)
Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammation; however, which Tlr4-expressing cells mediate this(More)
Studies have indicated that the neurotransmitter nitric oxide (NO) mediates leptin's effects in the neuroendocrine reproductive axis. However, the neurons involved in these effects and their regulation by leptin is still unknown. We aimed to determine whether NO neurons are direct targets of leptin and by which mechanisms leptin may influence neuronal NO(More)
The present study examined how muscle cross-sectional area (CSA) indices determined at rest and during maximal voluntary contraction (MVC) are related to muscle strength in middle-aged and elderly individuals (22 men and 36 women, 51-77 years). The muscle thickness (MT) of elbow flexors and circumference (C) at the level 60% distal to the upper arm was(More)
During the ontogenic change from fetal to adult human erythrocytes, as well as fetal haemoglobin being replaced by adult haemoglobin, the cell-surface antigen i is converted to I (ref. 1). Recently it has been shown that this antigenic change is the conversion of the linear repeating Gal beta 1 leads to 4GlcNac beta 1 leads to 3Gal structure to branched Gal(More)