Brian A. Droz

GCGR agonism requires GABAergic signaling in the medial basal hypothalamus to promote weight loss in obese mice

Andrew J. Elmendorf, Ellen C Furber, Betty Lorentz, Connor A. Mahler et autres

Glucagon receptor (GCGR)-mediated thermogenesis is a key component for the next-generation of obesity therapeutics. Herein, we investigated the central and peripheral mechanism by which activation of the GCGR augments metabolic rate to promote weight loss. Chronic treatment of obese mice with a …

us (code pays fourni par la source)

Tirzepatide Synergizes with Leptin on Weight Loss and Restoring Metabolic Homeostasis in Diet-induced Obesity Model

Xun Sun, Yuexi Yin, Min Song, Brian A. Droz et autres

Abstract Leptin resistance limits anti-obesity efficacy. We identified a leptin-sensitizing mechanism through tirzepatide (TZP), a glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonist. Our tirzepatide clinical trial revealed that circulating leptin levels at baseline correlated with weight loss efficacy …

us (code pays fourni par la source)

2180-LB: Bimagrumab Augments Metabolic Rate to Improve Incretin-Induced Weight Loss in Obese Mice

Jonquil M. Poret, Brian A. Droz, Eric D. Hawkins, Valentina Pirro et autres

Introduction and Objective: TGFβ-like ligands, such as myostatin, GDF3 and Activin E, signal via the activin type II receptors (ACVR2A/B) in skeletal muscle and adipose tissue to negatively impact muscle growth and promote excess adiposity. Hence, targeting the myostatin/activin pathway may provide …

us (code pays fourni par la source)

The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron

Kyle W. Sloop, Amy L. Cox, David B. Wainscott, Alex D. White et autres

Orally bioavailable, synthetic nonpeptide agonists (NPAs) of the glucagon-like peptide-1 receptor (GLP-1R) may offer an effective, scalable pharmacotherapy to address the metabolic disease epidemic. One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron, which is in clinical …

us (code pays fourni par la source)

The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice

Xinxin Yu, Shiuhwei Chen, Jan‐Bernd Funcke, Leon G. Straub et autres

us (code pays fourni par la source)

GIPR Agonism Enhances TZD-Induced Insulin Sensitivity in Obese IR Mice

Ellen C Furber, Karissa Hyatt, Kyla Collins, Xinxin Yu et autres

Recent studies have found that glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism can enhance the metabolic efficacy of glucagon-like peptide-1 receptor agonist treatment by promoting both weight-dependent and -independent improvements on systemic insulin sensitivity. These findings have prompted new investigations aimed at better …

us (code pays fourni par la source)

GIPR Agonism Enhances TZD-Induced Insulin Sensitivity in Obese IR Mice

Ellen C Furber, Karissa Hyatt, Kyla Collins, Xinxin Yu et autres

Recent studies have found that GIPR agonism can enhance the metabolic efficacy of GLP-1R agonist treatment by promoting both weight-dependent and -independent improvements on systemic insulin sensitivity. These findings have prompted new investigations aimed at better understanding the broad metabolic benefit of …

GIPR Agonism Enhances TZD-Induced Insulin Sensitivity in Obese IR Mice

Ellen C Furber, Karissa Hyatt, Kyla Collins, Xinxin Yu et autres

Recent studies have found that GIPR agonism can enhance the metabolic efficacy of GLP-1R agonist treatment by promoting both weight-dependent and -independent improvements on systemic insulin sensitivity. These findings have prompted new investigations aimed at better understanding the broad metabolic benefit of …

Tirzepatide induces a thermogenic-like amino acid signature in brown adipose tissue

Ricardo J. Samms, Guofang Zhang, Wentao He, Olga Ilkayeva et autres

OBJECTIVES: Tirzepatide, a dual GIP and GLP-1 receptor agonist, delivered superior glycemic control and weight loss compared to selective GLP-1 receptor (GLP-1R) agonism in patients with type 2 diabetes (T2D). These results have fueled mechanistic studies focused on understanding how tirzepatide achieves …

us (code pays fourni par la source)

GIPR Agonism Inhibits PYY-Induced Nausea-Like Behavior

Ricardo J. Samms, Richard A. Cosgrove, Brandy M. Snider, Ellen C Furber et autres

The induction of nausea and emesis is a major barrier to maximizing the weight loss profile of obesity medications, and therefore, identifying mechanisms that improve tolerability could result in added therapeutic benefit. The development of Peptide YY (PYY)-based approaches to treat obesity …

GIPR Agonism Inhibits PYY-Induced Nausea-Like Behavior

Ricardo J. Samms, Richard Cosgrove, Brandy M. Snider, Ellen C Furber et autres

The induction of nausea and emesis is a major barrier to maximizing the weight loss profile of obesity medications, and therefore, identifying mechanisms that improve tolerability could result in added therapeutic benefit. The development of peptide YY (PYY)-based approaches to treat obesity …

us (code pays fourni par la source)

GIPR Agonism Inhibits PYY-Induced Nausea-Like Behavior

Ricardo J. Samms, Richard A. Cosgrove, Brandy M. Snider, Ellen C Furber et autres

The induction of nausea and emesis is a major barrier to maximizing the weight loss profile of obesity medications, and therefore, identifying mechanisms that improve tolerability could result in added therapeutic benefit. The development of Peptide YY (PYY)-based approaches to treat obesity …