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We report the efficacy of a new peptide with agonism at the glucagon and GLP-1 receptors that has potent, sustained satiation-inducing and lipolytic effects. Selective chemical modification to glucagon resulted in a loss of specificity, with minimal change to inherent activity. The structural basis for the co-agonism appears to be a combination of local(More)
Diet-induced obesity and its serious consequences such as diabetes, cardiovascular disease, and cancer are rapidly becoming a major global health threat. Therefore, understanding the cellular and molecular mechanisms by which dietary fat causes obesity and diabetes is of paramount importance in order to identify preventive and therapeutic strategies.(More)
The identification of leptin as a mediator of body weight regulation provided much initial excitement for the treatment of obesity. Unfortunately, leptin monotherapy is insufficient in reversing obesity in rodents or humans. Recent findings suggest that amylin is able to restore leptin sensitivity and when used in combination with leptin enhances body(More)
Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol(More)
OBJECTIVE Apolipoprotein E (ApoE) regulates plasma lipid levels via modulation of lipolysis and serving as ligand for receptor-mediated clearance of triglyceride (TG)-rich lipoproteins. This study tested the impact of modulating lipid delivery to tissues on insulin responsiveness and diet-induced obesity. RESEARCH DESIGN AND METHODS ApoE(+/+) and(More)
OBJECTIVE Ghrelin, a stomach-derived, secreted peptide, and its receptor (growth hormone secretagogue receptor, GHSR) are known to modulate food intake and energy homeostasis. The ghrelin system is also expressed broadly in cardiovascular tissues. Since ghrelin has been associated with anti-inflammatory and anti-atherogenic properties, but is also well(More)
Targeted deletion of S6 kinase (S6K) 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed(More)
People exhibit a tendency to generalize a novel noun to the basic-level in a hierarchical taxonomy – a cognitively salient category such as “dog” – with the degree of generalization depending on the number and type of exemplars. Recently, a change in the presentation timing of exemplars has also been shown to have an effect, surprisingly reversing the prior(More)
A key challenge in vocabulary acquisition is learning which of the many possible meanings is appropriate for a word. The word generalization problem refers to how children associate a word such as dog with a meaning at the appropriate category level in a taxonomy of objects, such as Dalmatians, dogs, or animals. We present the first computational study of(More)
The authors briefly introduce a clinical outreach initiative that is innovative because of the types of partnerships that have been formed within an inner-city community context. The initiative was designed to foster access to primary health care and specialized services for children and families who are vulnerable because of their social and material(More)