Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents.

AIM: To investigate the role of glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists alone or combined with glucagon-like peptide-1 receptor (GLP-1R) agonists to regulate palatable food intake and the role of specific macronutrients in these preferences. METHODS: To understand this regulation, we treated mice and rats on several choice diet paradigms of chow and a palatable food option with individual or dual GIPR and GLP-1R agonists. RESULTS: In mice, the dual agonist tirzepatide suppressed total caloric intake, while promoting the intake of chow over a high fat/sucrose diet. Surprisingly, GIPR agonism alone did not alter food choice. The food intake shift observed with tirzepatide in wild-type mice was completely absent in GLP-1R knockout mice, suggesting that GIPR signalling does not regulate food preference. Tirzepatide also selectively suppressed the intake of palatable food but not chow in a rat two-diet choice model. This suppression was specific to lipids, as GLP-1R agonist and dual agonist treatment in rats on a choice paradigm assessing individual palatable macronutrients robustly inhibited the intake of Crisco (lipid) without decreasing the intake of a sucrose (carbohydrate) solution. CONCLUSIONS: Decreasing preference for high-caloric, high-fat foods is a powerful action of GLP-1R and dual GIPR/GLP-1R agonist therapeutics, which may contribute to the weight loss success of these drugs.

Seasonal variation in the bioaccumulation of potentially toxic metals in the tissues of Astrangia poculata in the northeastern United States.

Astrangia poculata inhabits coasts near dense human populations in the northeastern United States and may be exposed to elevated pollutants. No studies have assessed heavy metal concentration in temperate corals despite their proximity to anthropogenic activity. We collected colonies four times in one year and analyzed coral tissue for As, Cd, Cr, Pb, and Zn. Most heavy metals except for As were 1.5-3.3 times lower in summer compared to other seasons. Pb, As, and Cd were three orders of magnitude higher than concentrations for other Narragansett Bay benthic species, suggesting that A. poculata bioaccumulates more readily and/or inhabits more contaminated areas of the Bay. Zn, Pb, and As had similar concentrations to tropical corals inhabiting anthropogenically polluted sites. While physiological impacts are unknown, this population of A. poculata may have a higher tolerance for heavy metal pollution than most scleractinians, making it an interesting candidate for future studies.