Journal: Obesity (Silver Spring, Md.)

Article Title: Effects of a novel MC4R agonist on maintenance of reduced body weight in diet induced obese mice

doi: 10.1002/oby.20678

Figure Lengend Snippet: Schematic of protocol to assess the effects of a novel MC4R agonist (AZD2820) on maintenance of reduced body weight in DIO mice. Timepoints of physiological measurements and pharmacological treatment are indicated by arrows. WR - weight reduction, Body Comp - Body Composition, Calo - Calorimetry, Sac – Sacrifice, Time 0 – mice arrived at the Columbia facility and began the 5-week acclimatization period.

Article Snippet: In this study we examined the long term effects of a potent and selective cyclic peptide MC4R partial agonist (AZD2820; MC4R: EC 50 1nM in cAMP generation assay, 38% efficacy vs . NDP-α-MSH, and MC3R: binding K i 9nM, no agonist efficacy detected (AstraZeneca data on file) [ ] on induction of weight loss and on maintenance of reduced BW in diet induced obese (DIO) mice.

Techniques:

Journal: Obesity (Silver Spring, Md.)

Article Title: Effects of a novel MC4R agonist on maintenance of reduced body weight in diet induced obese mice

doi: 10.1002/oby.20678

Figure Lengend Snippet: Percent initial body weight post pump #1 implantation of mice fed a HFD throughout the study ( A ) and treated with MC4R agonist or vehicle and weight reduced by 20% prior to administration of the drug ( B ). Percent initial body weight in Medium-WR mice compared to High-AL group ( C ) and in Low-WR mice compared to Medium-AL group ( D ). Medium and low dose in WR mice is sufficient to maintain them at the same percentage initial body weight as AL mice treated with a high and medium dose of MC4R agonist, respectively. Mean initial body weight (g) [SEM] is given for each group in the figure legend ( A, B ) Nominal doses of AZD2820 - High : 53.4 nmol/day; Medium : 10.8 nmol/day; Low : 2.64 nmol/day. Each data point represents mean percent body weight for each group with SEM.

Article Snippet: In this study we examined the long term effects of a potent and selective cyclic peptide MC4R partial agonist (AZD2820; MC4R: EC 50 1nM in cAMP generation assay, 38% efficacy vs . NDP-α-MSH, and MC3R: binding K i 9nM, no agonist efficacy detected (AstraZeneca data on file) [ ] on induction of weight loss and on maintenance of reduced BW in diet induced obese (DIO) mice.

Techniques:

Journal: Obesity (Silver Spring, Md.)

Article Title: Effects of a novel MC4R agonist on maintenance of reduced body weight in diet induced obese mice

doi: 10.1002/oby.20678

Figure Lengend Snippet: Percent body weight change ( A ) or regain ( B ) at 12 weeks of drug treatment plotted individually for each mouse against plasma concentration of MC4R agonist. AL ( A ) and WR ( B ) mice are plotted separately. Black bars are % BW change means for each group. Note, the drug concentration (x-axis) is plotted on a log scale.

Article Snippet: In this study we examined the long term effects of a potent and selective cyclic peptide MC4R partial agonist (AZD2820; MC4R: EC 50 1nM in cAMP generation assay, 38% efficacy vs . NDP-α-MSH, and MC3R: binding K i 9nM, no agonist efficacy detected (AstraZeneca data on file) [ ] on induction of weight loss and on maintenance of reduced BW in diet induced obese (DIO) mice.

Techniques: Clinical Proteomics, Concentration Assay

Journal: Obesity (Silver Spring, Md.)

Article Title: Effects of a novel MC4R agonist on maintenance of reduced body weight in diet induced obese mice

doi: 10.1002/oby.20678

Figure Lengend Snippet: Fat Mass ( A, B ) and lean mass ( C, D ) in mice maintained on HFD ad lib throughout the study ( A, C ) or weight reduced by 20% prior to drug administration ( B, D ) measured prior to and 12 weeks after MC4R agonist treatment. Formerly WR mice given high nominal drug dose (53.4 nmol/day) achieved a significantly lower body fat than the controls after an 8 week body weight regain period. Nominal doses of AZD2820 - High : 53.4 nmol/day; Medium : 10.8 nmol/day; Low : 2.64 nmol/day. Each data point represents mean fat mass or lean (fat free mass) for each group with SEM. *P < 0.05 between vehicle and high dose treated groups by Student’s t-test.

Article Snippet: In this study we examined the long term effects of a potent and selective cyclic peptide MC4R partial agonist (AZD2820; MC4R: EC 50 1nM in cAMP generation assay, 38% efficacy vs . NDP-α-MSH, and MC3R: binding K i 9nM, no agonist efficacy detected (AstraZeneca data on file) [ ] on induction of weight loss and on maintenance of reduced BW in diet induced obese (DIO) mice.

Techniques:

Journal: Obesity (Silver Spring, Md.)

Article Title: Effects of a novel MC4R agonist on maintenance of reduced body weight in diet induced obese mice

doi: 10.1002/oby.20678

Figure Lengend Snippet: Circulating leptin concentrations (ng/ml) in mice maintained on HFD ad lib throughout the study ( A ) or weight reduced by 20% prior to drug administration ( B ) measured at different timepoints during the study. As expected from the fat mass data, circulating leptin levels are lower in high dose treated animals (both AL and WR) after at least 11 weeks of treatment. Regression of circulating leptin (ng/ml) against fat mass (g) in all mice at 4 weeks ( C ) and 12 weeks ( D ) of MC4R agonist treatment. The circle denotes WR mice which have an increased plasma leptin concentrations relative to fat mass compared to the vehicle treated AL mice. This effect is independent of MC4R agonist treatment and is reversed after formerly WR mice had returned to AL feeding for 8 weeks ( D ). Nominal doses of AZD2820 - High : 53.4 nmol/day; Medium : 10.8 nmol/day; Low : 2.64 nmol/day. Each data point represents mean value for each group with SEM. *P < 0.05 between vehicle and high dose treated groups by Student’s t-test.

Article Snippet: In this study we examined the long term effects of a potent and selective cyclic peptide MC4R partial agonist (AZD2820; MC4R: EC 50 1nM in cAMP generation assay, 38% efficacy vs . NDP-α-MSH, and MC3R: binding K i 9nM, no agonist efficacy detected (AstraZeneca data on file) [ ] on induction of weight loss and on maintenance of reduced BW in diet induced obese (DIO) mice.

Techniques: Clinical Proteomics

Journal: Obesity (Silver Spring, Md.)

Article Title: Effects of a novel MC4R agonist on maintenance of reduced body weight in diet induced obese mice

doi: 10.1002/oby.20678

Figure Lengend Snippet: Absolute total ( A ) and resting ( B ) energy expenditure (kcal/24h) measured at 12–13 weeks of drug treatment and immediately prior to sacrifice by indirect calorimetry (TSE LabMaster system). No significant difference was found in absolute total and resting EE among treatment groups. Body Composition in AL mice ( C ) and formerly WR mice ( D ) at 12 weeks of drug treatment. Formerly WR mice treated with high dose of MC4R agonist have a significantly lower BW and fat mass but show the same TEE and REE. ( E ) Resting energy expenditure (kcal/24h) per unit of lean mass (g) measured at 12–13 weeks of drug treatment and immediately prior to sacrifice by indirect calorimetry (TSE LabMaster system). Nominal doses of AZD2820 - High : 53.4 nmol/day; Medium : 10.8 nmol/day; Low : 2.64 nmol/day. *P < 0.05 between vehicle and high dose treated groups by Student’s t-test.

Article Snippet: In this study we examined the long term effects of a potent and selective cyclic peptide MC4R partial agonist (AZD2820; MC4R: EC 50 1nM in cAMP generation assay, 38% efficacy vs . NDP-α-MSH, and MC3R: binding K i 9nM, no agonist efficacy detected (AstraZeneca data on file) [ ] on induction of weight loss and on maintenance of reduced BW in diet induced obese (DIO) mice.

Techniques: