A peptidomimetic that targets prohibitin in white adipose tissue vasculature, inducing apoptosis and leading to rapid weight loss and improved insulin sensitivity.
Preiss. David D; Dawed. Adem A; Welsh. Paul P; Heggie. Alison A; Jones. Angus G AG; Dekker. Jacqueli...
Taking metformin regularly raises your fasting GLP-1 hormone levels and keeps them higher for at least a year and a half, even if you don’t lose weight or change your blood sugar. This effect shows up in people without diabetes and also in newly diagnosed diabetics, and it’s not just a short‑term spike after a meal.
Barnhart. Kirstin F KF; Christianson. Dawn R DR; Hanley. Patrick W PW; Driessen. Wouter H P WH; Bern...
In a study with obese monkeys, a synthetic peptide called adipotide was injected and caused the blood vessels that feed white fat cells to die. This led to a quick drop in body fat and better blood‑sugar control. The treatment also caused temporary, reversible changes in kidney function, showing both promise and safety concerns.
Kim. Dong-Hoon DH; Sartor. Maureen A MA; Bain. James R JR; Sandoval. Darleen D; Stevens. Robert D RD...
A specially designed peptide called adipotide can kill cells lining the blood vessels in white fat tissue. In obese mice, a short‑term dose of this peptide made the animals handle sugar much better, even though they didn’t lose weight or eat less. It also lowered insulin and blood fats and changed several metabolic pathways back toward a healthier state.
Hossen. Nazir N; Kajimoto. Kazuaki K; Akita. Hidetaka H; Hyodo. Mamoru M; Harashima. Hideyoshi H
In mice that are obese from a high‑fat diet, a tiny particle that carries a cell‑killing peptide (KLA) and homes in on fat‑blood vessels shrank their weight and lowered harmful fat deposits better than the older peptide‑only drug called Adipotide. The treatment also lowered leptin, raised the healthy hormone adiponectin, and didn’t hurt the liver.
A study showed that a peptide called adipotide made obese monkeys lose weight, and the original authors said it worked by killing blood vessels that feed white fat. However, a comment on the paper argues the weight loss might actually be because the monkeys ate less, not because the peptide directly destroyed fat tissue.
Sharma. Geetanjali G; Hu. Chelin C; Staquicini. Daniela I DI; Brigman. Jonathan L JL; Liu. Meilian M...
Human obesity has become a global health epidemic, with few safe and effective pharmacological therapies currently available. The systemic loss of ovarian estradiol (E2) in women after menopause greatly increases the risk of obesity and metabolic dysfunction, revealing the critical role of E2 in this setting. The salutary effects of E2 are traditionally attributed to the classical estrogen receptors ERα and ERβ, with the contribution of the G protein-coupled estrogen receptor (GPER) still largely unknown. Here, we used ovariectomy- and diet-induced obesity (DIO) mouse models to evaluate the preclinical activity of GPER-selective small-molecule agonist G-1 (also called Tespria) against obesity and metabolic dysfunction. G-1 treatment of ovariectomized female mice (a model of postmenopausal obesity) reduced body weight and improved glucose homeostasis without changes in food intake, fuel source usage, or locomotor activity. G-1-treated female mice also exhibited increased energy expenditure, lower body fat content, and reduced fasting cholesterol, glucose, insulin, and inflammatory markers but did not display feminizing effects on the uterus (imbibition) or beneficial effects on bone health. G-1 treatment of DIO male mice did not elicit weight loss but prevented further weight gain and improved glucose tolerance, indicating that G-1 improved glucose homeostasis independently of its antiobesity effects. However, in ovariectomized DIO female mice, G-1 continued to elicit weight loss, reflecting possible sex differences in the mechanisms of G-1 action. In conclusion, this work demonstrates that GPER-selective agonism is a viable therapeutic approach against obesity, diabetes, and associated metabolic abnormalities in multiple preclinical male and female models.
Huang. Rae-Chi RC; Lillycrop. Karen A KA; Beilin. Lawrence J LJ; Godfrey. Keith M KM; Anderson. Deni...
"Accelerated aging," assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age.
DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers] were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development.
In 995 participants (49.6% female; age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ-inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors.
Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.