Research Advances

New research reveals that obesity in female mice leads to stress signals that reduce transmission of mitochondria to offspring. At the fetal stage, these offspring are heavier than normal  and have reduced liver and kidney mitochondrial DNA content per cell. Treating the obese female mice with certain stress inhibitors that are being studied for the treatment of diabetes and other conditions restored egg quality, embryo development, and mitochondrial DNA levels. The findings are published in the journal Development.

Scientists have found that impairment of a pathway called chaperone-mediated autophagy (CMA) plays a role in cystinosis, a lysosomal storage disorder that can cause eye and kidney damage. During CMA, chaperone proteins seek out proteins marked by specific amino acid tags and ferry them to lysosomes, where they are ingested and recycled. Concentrations of LAMP2A, a lysosomal surface protein that interacts with chaperone proteins to facilitate the translocation of molecules across the lysosomal membrane, were down by 50% to 80% in cystinotic cells.

Rats that were given 20 times their recommended daily amount of folic acid throughout mating, pregnancy, and lactation gave birth to offspring that became overweight and insulin resistant in adulthood. The offspring also grew up to be deficient in adiponectin (a hormone that protects against diabetes and obesity) and had irregular feeding behaviors. These symptoms were more pronounced in female adult offspring. The offspring of rats that consumed the recommended daily amount of folic acid were healthy as adults.

By analyzing genetic samples from 339,224 individuals, researchers found 97 locations across the genome that are linked with individuals’ BMI. Many locations have significant effects on various aspects of metabolism. The 97 loci account for approximately 2.7% of BMI variation, and genomewide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses suggest the central nervous system plays an important role in obesity susceptibility.

The enzyme heme oxygenase-1 (HO-1) is known to be important in the body’s protective response against AKI. Researchers have now found that HO-1 helps to direct a specific subset of immune cells, called myeloid cells, as they traffic to and from the kidney after it is injured. In mice, the absence of HO-1 led to poor recovery after AKI. The JASN findings could lead to new treatments for patients with AKI.

In experiments done in spontaneously hypertensive rats, both coconut oil and exercise training over 5 weeks were able to reduce weight gain. Also, either coconut oil supplementation or exercise training was shown to reduce blood pressure; however, only combined coconut oil and exercise training brought levels back to normotensive values.

A murine model revealed a clear linkage between vascular calcification and reduced levels of a specific microRNA molecule, miR-30e. Expression of miR-30e led to repression of an osteogenic gene panel including Igf2, while injections of antimiR-30e molecules increased Igf2 expression in the aortas and livers and significantly enhanced calcium deposition in aortic valves. MiR-30e repressed the osteogenic program in mesenchymal stem cells and aortic smooth muscle cells, and drove their differentiation into adipogenic, or smooth muscle lineages, respectively.

An antibody abundant in mice (IgG1, which resembles IgG4 in humans) offers poor assistance in fighting against infections, but it may play a key role in preventing self-inflicted forms of kidney disease. A Nature study found IgG1 is unable to clump pathogens, activate complement, and activate cells by binding to their Fc receptors.

Previously, researchers found that gut bacteria convert L-carnitine (a nutrient found in red meat) into trimethylamine, which promotes atherosclerosis. Now, the team has found that gamma-butyrobetaine is produced as an intermediary metabolite by microbes after L-carnitine is ingested, and it contributes to atherosclerosis as well. Gamma-butyrobetaine is produced by microbes at a rate that is 1000-fold higher than the formation of trimethylamine.

Pentaerythritol tetranitrate (PETN), an explosive compound in the same chemical family as nitroglycerin and nitrocellulose (components of dynamite and gunpowder), may prevent hypertension from developing in the female offspring of rats with the condition. According to the Hypertension study, pregnant hypertensive rats consumed 50 mg of PETN for every 1 kg of body weight each day throughout pregnancy and lactation.

Statin treatment can reverse learning disabilities in a mouse model of Noonan syndrome, a developmental disorder that causes unusual facial features, stunted growth, and heart problems. About half of all people with Noonan also have learning deficits. Researchers discovered that the mutated gene implicated in Noonan syndrome creates hyperactive Ras, which has a disruptive effect on brain cell communication. Mice treated with lovastatin had a drop in Ras activity and a corresponding improvement in their ability to navigate mazes and remember objects.

In a nationally representative study, survivors of heart attack gained approximately 1.5 to 3.5 new functional limitations (or problems with performing daily tasks) over 10 years, and survivors of stroke gained approximately 3.5 to 4.5 limitations. The risk of developing severe depressive symptoms were 20% greater for every new functional limitation gained after having a heart attack and 34% greater for every new functional limitation gained after having a stroke.