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Supercharging proteins can impart unusual resilience.
TLDR
“supercharging” the surface of three disparate proteins to alter their net charge by as much as 55 charge units, without destroying protein folding or function is demonstrated, demonstrating an approach to increasing protein robustness and suggesting surprisingly broad, untapped plasticity at protein surfaces.
Peroxisome Proliferator-Activated Receptor γ Is a Target for Halogenated Analogs of Bisphenol A
TLDR
The results strongly suggest that polyhalogenated bisphenols could function as obesogens by acting as agonists to disrupt physiological functions regulated by human or animal PPARγ.
Asprosin is a centrally-acting orexigenic hormone
TLDR
It is demonstrated that asprosin in the circulation crosses the blood–brain barrier and directly activates orexigenic AgRP+ neurons via a cAMP-dependent pathway, which results in inhibition of downstream anorexigenic proopiomelanocortin-positive neurons in a GABA-dependent manner, which leads to appetite stimulation and a drive to accumulate adiposity and body weight.
Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) γ Activators and Pan-PPAR Partial Agonists
TLDR
It is proposed that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPARγ modulators with useful clinical profiles among natural products.
Gaining ligand selectivity in thyroid hormone receptors via entropy
TLDR
It is proposed that increased solvation compensates for weaker interactions of ligand with TRβ and permits greater flexibility of the Triac carboxylate group in TRβ than in TRα, resulting in lower entropic restraint and decreases free energy of interactions between Triac and TRβ, explaining subtype-selective binding.
Asprosin is a centrally acting orexigenic hormone
TLDR
It is demonstrated that plasma asprosin crosses the blood-brain-barrier and directly activates orexigenic AgRP+ neurons via a cAMP-dependent pathway, resulting in appetite stimulation and a drive to accumulate adiposity and body weight.
Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
TLDR
A unique mechanism of ligand-mediated DNA site recognition is suggested, whereby metallocluster ligation relocates a protein-specificity determinant to expand DNA target-site selection, allowing a broader transcriptomic response by holo-IscR.
GQ-16, a Novel Peroxisome Proliferator-activated Receptor γ (PPARγ) Ligand, Promotes Insulin Sensitization without Weight Gain
TLDR
The results suggest that the emerging model, whereby “ideal” PPARγ-based therapeutics stabilize the β-sheet/Ser-273 region and inhibit Cdk5-mediated phosphorylation while minimally invoking adipogenesis and classical agonism, is indeed a valid framework to develop improved PParγ modulators that retain antidiabetic actions while minimizing untoward effects.
Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways.
TLDR
Although both GC-1 and KB-2115 potently treat hepatic steatosis in fat-fed rats, they each worsen insulin action via specific and discrete mechanisms, which means the development of future TRβ agonists must consider the potential adverse effects on insulin sensitivity.
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