Faculty Opinions recommendation of Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice.

Long-acting glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists (GLP-1RA), such as exendin-4 (Ex4), promote weight loss. On the basis of a newly discovered interaction between GLP-1 and oleoylethanolamide (OEA), we tested whether OEA enhances GLP-1RA-mediated anorectic signaling and weight loss. We analyzed the effect of GLP-1+OEA and Ex4+OEA on canonical GLP-1R signaling and other proteins/pathways that contribute to the hypophagic action of GLP-1RA (AMPK, Akt, mTOR, and glycolysis). We demonstrate that OEA enhances canonical GLP-1R signaling when combined with GLP-1 but not with Ex4. GLP-1 and Ex4 promote phosphorylation of mTOR pathway components, but OEA does not enhance this effect. OEA synergistically enhanced GLP-1- and Ex4-stimulated glycolysis but did not augment the hypophagic action of GLP-1 or Ex4 in lean or diet-induced obese (DIO) mice. However, the combination of Ex4+OEA promoted greater weight loss in DIO mice than Ex4 or OEA alone during a 7-day treatment. This was due in part to transient hypophagia and increased energy expenditure, phenotypes also observed in Ex4-treated DIO mice. Thus, OEA augments specific GLP-1RA-stimulated signaling but appears to work in parallel with Ex4 to promote weight loss in DIO mice. Elucidating cooperative mechanisms underlying Ex4+OEA-mediated weight loss could, therefore, be leveraged toward more effective obesity therapies.

Download Full-text

Expression of eotaxin in 3T3-L1 adipocytes and the effects of weight loss in high-fat diet induced obese mice

Nutrition Research and Practice ◽

10.4162/nrp.2011.5.1.11 ◽

2011 ◽

Vol 5 (1) ◽

pp. 11 ◽

Cited By ~ 7

Author(s):

Hyun-Jung Kim ◽

Chang-Hyun Kim ◽

Do-Hyun Lee ◽

Min-Woo Han ◽

Mi-Young Kim ◽

...

Keyword(s):

Weight Loss ◽

High Fat Diet ◽

Obese Mice ◽

High Fat

Download Full-text

Chronic C75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00261.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. E97-E104 ◽

Cited By ~ 50

Author(s):

Jagan N. Thupari ◽

Eun-Kyoung Kim ◽

Timothy H. Moran ◽

Gabriele V. Ronnett ◽

Francis P. Kuhajda

Keyword(s):

Weight Loss ◽

Fatty Acid ◽

Food Consumption ◽

Fatty Acid Synthase ◽

Acid Oxidation ◽

Obese Mice ◽

Sustained Weight Loss ◽

Cpt I ◽

Adipose Mass

Obesity and its attendant disorders, such as type 2 diabetes, are global health problems. We previously reported that C75, an inhibitor of fatty acid synthase (FAS) and stimulator of carnitine palmitoyltransferase I (CPT I), caused anorexia and profound weight loss in lean and genetically obese mice. To approximate human obesity, we utilized a chronic C75 treatment model for diet-induced obese (DIO) mice. Chronic C75 treatment decreased food consumption and increased energy expenditure due to increased fatty acid oxidation in both DIO and lean mice. There was a substantial loss of adipose tissue and resolution of hepatic steatosis in C75-treated DIO mice. Analysis of changes in the expression of hypothalamic neuropeptides demonstrated that the reduced food consumption in C75-treated DIO mice was accompanied by an increase in cocaine and amphetamine-related transcript expression but not by changes in neuropeptide Y such as seen with acute C75 treatment of lean mice. Inhibition of FAS and stimulation of CPT I provide a means to achieve stable, sustained weight loss in DIO mice.

Download Full-text

OR28-5 Bile Acid Sequestration Accelerates Glucagon Receptor-Mediated Body Weight Loss in Obese Mice

Journal of the Endocrine Society ◽

10.1210/js.2019-or28-5 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Teayoun Kim ◽

Shelly Nason ◽

Jessica Antipenko ◽

Natalie Presedo ◽

Brian Finan ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Bile Acid ◽

Body Weight Loss ◽

Obese Mice ◽

Glucagon Receptor

Download Full-text

Short-term strength training reduces gluconeogenesis and NAFLD in obese mice

Journal of Endocrinology ◽

10.1530/joe-18-0567 ◽

2019 ◽

Vol 241 (1) ◽

pp. 59-70 ◽

Cited By ~ 8

Author(s):

Rodrigo Martins Pereira ◽

Kellen Cristina da Cruz Rodrigues ◽

Chadi Pellegrini Anaruma ◽

Marcella Ramos Sant’Ana ◽

Thaís Dantis Pereira de Campos ◽

...

Keyword(s):

Weight Loss ◽

Insulin Sensitivity ◽

Strength Training ◽

Term Strength ◽

Obese Mice ◽

Short Term ◽

Fat Accumulation ◽

Hepatic Insulin Sensitivity ◽

Short Term Strength ◽

Hepatic Fat

Non-alcoholic fatty liver disease (NAFLD) has a positive correlation with obesity, insulin resistance and type 2 diabetes mellitus (T2D). The aerobic training is an important tool in combating NAFLD. However, no studies have demonstrated the molecular effects of short-term strength training on the accumulation of hepatic fat in obese mice. This study aimed to investigate the effects of short-term strength training on the mechanisms of oxidation and lipid synthesis in the liver of obese mice. The short duration protocol was used to avoid changing the amount of adipose tissue. Swiss mice were separated into three groups: lean control (CTL), sedentary obese (OB) and strength training obese (STO). The obese groups were fed a high-fat diet (HFD) and the STO group performed the strength training protocol 1 session/day for 15 days. The short-term strength training reduced hepatic fat accumulation, increasing hepatic insulin sensitivity and controlling hepatic glucose production. The obese animals increased the mRNA of lipogenic genes Fasn and Scd1 and reduced the oxidative genes Cpt1a and Ppara. On the other hand, the STO group presented the opposite results. Finally, the obese animals presented higher levels of lipogenic proteins (ACC and FAS) and proinflammatory cytokines (TNF-α and IL-1β), but the short-term strength training was efficient in reducing this condition, regardless of body weight loss. In conclusion, there was a reduction of obesity-related hepatic lipogenesis and inflammation after short-term strength training, independent of weight loss, leading to improvements in hepatic insulin sensitivity and glycemic homeostasis in obese mice. Key points: (1) Short-term strength training (STST) reduced fat accumulation and inflammation in the liver; (2) Hepatic insulin sensitivity and HPG control were increased with STST; (3) The content and activity of ACC and content of FAS were reduced with STST; (4) STST improved hepatic fat accumulation and glycemic homeostasis; (5) STST effects were observed independently of body weight change.

Download Full-text

Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss

Journal of Cellular Physiology ◽

10.1002/jcp.23037 ◽

2012 ◽

Vol 227 (7) ◽

pp. 2917-2926 ◽

Cited By ~ 40

Author(s):

R. Marinho ◽

E.R. Ropelle ◽

D.E. Cintra ◽

C.T. De Souza ◽

A.S.R. Da Silva ◽

...

Keyword(s):

Weight Loss ◽

Exercise Training ◽

Endurance Exercise ◽

Insulin Signaling ◽

Hepatic Tissue ◽

Obese Mice ◽

Endurance Exercise Training

Download Full-text

Abstract 17023: Adipose Tissue Specific Temporal Deletion of Ager Induces Weight Loss in Diet Induced Obese Mice and Improves Glucose Homeostasis

Circulation ◽

10.1161/circ.142.suppl_3.17023 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Robin Wilson ◽

Lakshmi Arivazhagan ◽

Henry Ruiz ◽

Jay Pendse ◽

Laura Frye ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Glucose Homeostasis ◽

Fasting Glucose ◽

Obese Mice ◽

Gene Encoding ◽

Low Fat Diet ◽

Insulin Tolerance ◽

Specific Deletion

Introduction: The incidence of obesity and its comorbidities is increasing at an alarming rate in US and around the globe. Our previous studies showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance (IR), as global Ager (gene encoding RAGE) and adipocyte-specific Ager- deleted mice fed a high fat diet (HFD) showed protection from weight gain and IR. However, the role of Ager deletion in mice with established obesity, switched to low fat diet has not been tested. We hypothesize that temporal adipocyte-specific deletion of Ager in obese mice could enhance weight loss and improves glucose homeostasis. Methods: Mice with conditional adipocyte-specific Ager deletion were generated by breeding Ager flox/flox mice with AdipoQ ERT2 Cre recombinase mice resulting in Ager flox/flox / AdipoQ ERT2 Cre (+) and Cre (-) animals. Mice were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity and were then treated with tamoxifen (TAM) (75 mg/kg per day x 3 alternative days) to induce deletion of Ager . After 4 weeks of TAM treatment, mice were switched to standard chow for 7 weeks and body weight was monitored regularly. Fasting glucose, insulin and glucose tolerance was measured. Results: After 7 weeks of switching to standard chow following TAM, Cre (+) lost significantly more body weight whereas Cre (-) mice showed no significant weight loss over 7 weeks. Furthermore, Cre (+) mice exhibited significantly higher food intake, lower fasting glucose, lower epididymal and inguinal white adipose tissue weights, and improved glucose and insulin tolerance compared to Cre (-) mice. Conclusions: Temporal adipocyte-specific deletion of Ager in mice with established obesity promotes weight loss and improves glucose homeostasis. RAGE may act as a novel therapeutic target in obesity.

Download Full-text

Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.6.r1518 ◽

1998 ◽

Vol 274 (6) ◽

pp. R1518-R1525 ◽

Cited By ~ 2

Author(s):

Atsushi Kaibara ◽

Armin Moshyedi ◽

Troy Auffenberg ◽

Amer Abouhamze ◽

Edward M. Copeland ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Food Intake ◽

Acute Phase ◽

Acute Phase Response ◽

Acute Phase Protein ◽

Obese Mice ◽

Preferential Loss ◽

Phase Protein ◽

Protein Response

The ob gene product leptin is known to produce anorexia and loss of body fat when chronically administered to both lean and genetically obese mice. The current study was undertaken to examine whether administration of recombinant leptin in quantities sufficient to produce decreases in food intake and body weight and alterations in body composition would elicit either an hepatic acute phase protein response or preferential loss of carcass lean tissue. Mice were administered increasing quantities of recombinant human leptin or human tumor necrosis factor-α as a positive control. Although leptin (at 10 mg/kg body wt) produced significant anorexia and weight loss (both P < 0.05), human leptin administration did not appear to induce an hepatic acute phase protein response in either lean or genetically obese mice, as determined by protein synthetic rates in the liver or changes in the plasma concentration of the murine acute phase protein reactants, amyloid A, amyloid P, or seromucoid (α1-acid glycoprotein). In addition, human leptin administration did not induce a loss of fat-free dry mass (protein) in lean or obese animals. The findings suggest that at doses adequate to alter food intake and body weight leptin is not a significant inducer of the hepatic acute phase response nor does leptin promote the preferential loss of somatic protein characteristic of a chronic inflammatory process.

Download Full-text