Image by Bob Dmyt from Pixabay

Decmeber 2nd, 2022

None of these VOC's are showing signs of increased disease morbidity.


Little else to report here. (CDC Variants)

 Quick Hits and other musings -

1) Boring week - nothing to report this week on covid!

2) Science heavy but an explanation for certain humans that struggle with weight gain: "Here we report a heterozygous tandem duplication at the ASIP (agouti signaling protein) gene locus causing ubiquitous, ectopic ASIP expression in a female patient with extreme childhood obesity. The mutation places ASIP under control of the ubiquitously active itchy E3 ubiquitin protein ligase promoter, driving the generation of ASIP in patient-derived native and induced pluripotent stem cells for all germ layers and hypothalamic-like neurons.

The patient’s phenotype of early-onset obesity, overgrowth, red hair and hyperinsulinemia is concordant with that of mutant mice ubiquitously expressing the homolog nonagouti. ASIP represses melanocyte-stimulating hormone-mediated activation as a melanocortin receptor antagonist, which might affect eating behavior, energy expenditure, adipocyte differentiation and pigmentation, as observed in the index patient. As the type of mutation escapes standard genetic screening algorithms, we rescreened the Leipzig Childhood Obesity cohort of 1,745 patients and identified four additional patients with the identical mutation, ectopic ASIP expression and a similar phenotype. Taken together, our data indicate that ubiquitous ectopic ASIP expression is likely a monogenic cause of human obesity." (Kempf et. al. 2022)

This research is akin to the mouse research of Dr. Randy Jirtle, Podcast #2, whereby he discussed the epigenetically affected gene locus that leads to mice with a propensity to gain weight uncontrolled, have diabetes and a massive risk of cancer. It turns out that some humans have this gene as well which is a terrible problem in a modern world where calories are easily obtained.

3) From the Journal Nature we see a study discussing how routine exercise which is known to provide a wide range of beneficial effects for healthy physiology can be influenced by intestinal microbes driving neuro chemical motivation. There exists a gut–brain connection in a mouse animal model that enhances exercise performance by augmenting dopamine signaling during physical activity. The authors discovered that a microbiome based increase in endo-cannabinoid metabolites can stimulate the use of "TRPV1-expressing sensory neurons" and thereby elevateing dopamine levels in the brain during exercise. They further showed that by stimulating this pathway running performance is enhanced. On the flip side, microbiome depletion, endo-cannabinoid receptor inhibition or the destruction of spinal afferent neurons will reduce exercise capacity. (Dohnalova et. al. 2022)

Fascinating data set showing yet again how critical the intestinal microbiome is to our desires and then actions that lead to health.

4) Association between gut microbiota and mineral metabolism - Gut microbes interact with minerals and the human body in many positive ways. They help to protect the colonic mucosa from damage of iron induced oxidative damage. They help with absorption of minerals involved in bone synthesis. (Skrypnik et. al. 2017) The end result of a healthy cohort of gut microbes is improved metabolism and cofactor activity.


Time restricted feeding and fasting:

5) In a new study, we see emerging research that indicates that one mechanism whereby time restricted eating may confer health benefits is by "influencing the expression of the epigenetic modulator circulatory miRNAs, which serve as intercellular communicators and are dysregulated in metabolic disorders, such as obesity". Micro RNA is small genetic material with ability to alter gene expression leading to differential protein signaling and metabolism. "....the targets of downregulated miRNAs were associated with Ras signaling (cell growth and proliferation), mTOR signaling (cell growth and protein synthesis), insulin signaling (glucose uptake), and autophagy (cellular homeostasis and survival)." The authors found that time restricted eating led to down regulation of certain micro RNAs leading to inhibited metabolic pathways involved in cell survival, cell growth and the avoidance of cellular senescence. (Saini et. al. 2022)

6) Timing of restricted eating had the greatest impact on eating when the food was localized to consumption in the early part of the day, i.e. breakfast and lunch. (Martinez C. 2022) This is likely due to chronobiology and the effects of daytime gene protein activity leading to improved metabolism. Overall, however, time restricted feeding is a benefit regardless of time because people are more likely to consume less calories. If you have a choice, eat earlier. However, the choice to eat more often versus restricted is a clear one. Eat less frequently and less food overall.

That's all this week - a quick one!

Dr. M

Kempf Nature Metabolism
Dohnalova Nature
Skrypnik J Science of Food and Agriculture
Martinez Medscape
Saini Nutrients
CDC Variants Page
CDC Covid Deaths