Effects of the administration of angiotensin II on cardiac glycogen metabolism in the rat.

Changes in glycogen metabolism after an intravenous injection of angiotensin II were investigated in the left and right ventricles of the rat heart, as a function of location within the ventricular wall. Hearts were cut into 100-microns thin section, all of which were analysed for glycogen content, glucose incorporation into glycogen and 2-deoxyglucose uptake and phosphorylation after the intravenous injection of 14C-labelled sugar. In control hearts, glycogen levels were uniform across the wall in both ventricles, while the rate of sugar uptake and phosphorylation, and that of glucose incorporation into glycogen, were significantly higher in the subendocardial myocardium of the left ventricular wall. After angiotensin II administration, heart glycogen levels decreased slightly in the left, but not in the right ventricle, while 2-deoxyglucose uptake and phosphorylation, and glucose incorporation into glycogen, increased 2,5- and 5-fold, respectively. With regard to the distribution across the wall of the left ventricle after angiotensin administration, glycogen levels and glucose incorporation into glycogen were uniformly distributed, whereas sugar phosphorylation was still higher in the subendocardium

ENDOCRINE AND AMINO-ACID REGULATION OF LIVER MACROAUTOPHAGY AND PROTEOLYTIC FUNCTION

Endocrine and amino acid regulation of liver macroautophagy and proteolytic function. Am, J. Physiol. 266 (Gastrointest. Liver Physiol. 29): G118-G122, 1994.-Regulation of liver macroautophagy and protein degradation by hormones and direct regulatory amino acids were studied in male 2-mo-old Sprague-Dawley albino rats with the use of the antilipolytic agent 3,5'-dimethylpyrazole (DMP; 12 mg/kg body wt ip) as a stimulatory agent. Injection of DMP decreased glutamine plasma levels and glutamine release from the perfused liver. Autophagic vacuoles were observed in the pericanalicular area of liver cells after 30 min. Levels and release of other regulatory amino acids did not exhibit any significant decrease but subsequently increased. Intraperitoneal administration of glutamine inhibited the proteolytic response. In conclusion, these studies demonstrate that in vivo induction and control of liver macroautophagy and protein degradation by the physiological mechanism (i.e., by shortage of nutrients) involve unbalanced and asynchronous changes in the levels of selected direct regulatory amino acids (i.e., a decrease in glutamine and a subsequent increase in leucine and tyrosine levels)

Identification and validation of common molecular targets of hydroxytyrosol

Hydroxytyrosol (HT) is involved in healthful activities and is beneficial to lipid metabolism. Many investigations focused on finding tissue-specific targets of HT through the use of different omics approaches such as transcriptomics and proteomics. However, it is not clear which (if any) of the potential molecular targets of HT reported in different studies are concurrently affected in various tissues. Following the bioinformatic analyses of publicly available data from a selection of in vivo studies involving HT-supplementation, we selected differentially expressed lipid metabolism-related genes and proteins common to more than one study, for validation in rodent liver samples from the entire selection. Four miRNAs (miR-802-5p, miR-423-3p, miR-30a-5p, and miR-146b-5p) responded to HT supplementation. Of note, miR-802-5p was commonly regulated in the liver and intestine. Our premise was that, in an organ crucial for lipid metabolism such as the liver, consistent modulation should be found for a specific target of HT even if different doses and duration of HT supplementation were used in vivo. Even though our results show inconsistency regarding differentially expressed lipid metabolism-related genes and proteins across studies, we found Fgf21 and Rora as potential novel targets of HT. Omics approaches should be fine-tuned to better exploit the available databases

Autophagy fights disease through cellular self-digestion

Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62766/1/nature06639.pd

Transmural differences of lipofuscin pigment accumulation in the left ventricule of rat heart during growth and aging.

In view of the higher metabolic rate in subendocardial heart tissue, the rate of age-related lipofuscin pigment accumulation was explored in different regions of the left ventricle heart wall of Sprague-Dawley rats. Hearts were removed from 2-, 6-, 12- and 24-month-old rats, and lipofuscin pigment accumulation was assessed in the subepicardial and subendocardial layers, either by measuring extractable fluorescent material, or by direct visualization with fluorescence microscopy. Findings showed that the amount of extractable fluorescent material and the number, size and brightness of the fluorescent lipofuscin granules increased with age in all the myocardial tissue layers. The rate of accumulation of extractable fluorescent material was higher in subendocardial compared to subepicardial tissue. At the microscope, fluorescent granules exhibited a different morphological appearance in the subendocardial and subepicardial tissue of the two older age-groups. These data support the hypothesis that liposoluble age-pigment deposition is linked to the rate of local oxidative metabolism

Changes in the transmural distribution of antioxidant enzyme activities across the left ventricle heart wall from rats fed ad libitum or food-restricted during growth and aging.

Data on vulnerability to injury and on the larger age-related accumulation of lipofuscin in the subendocardial myocardium prompted us to investigate the changes in the levels and in the transmural distribution of catalase (C), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities across the left ventricle heart wall of rats fed ad libitum a standard diet or submitted to intermittent feeding during growth and aging. Enzyme activities were assayed by standard techniques on subepicardial, midmyocardial or subendo- cardial tissue obtained by cutting the heart wall into 100-microm-thick sections at the cryostat. The levels of GSH-Px and of C (but not of SOD) activity increased with age and reached their highest values in the subendocardial region by adulthood or senescence, respectively. No effect was observed of intermittent feeding on age-related changes in enzyme levels and transmural distribution

The brown adipose tissue of hyperthyroid rats. A biochemical and ultrastructural study.

Male Sprague-Dawley rats were treated with triiodothyronine (100 micrograms/100 g/day) for 2, 4, 7, 14 and 21 days and the biochemical and ultrastructural changes of the brown adipose tissue were investigated. Results showed that the tissue weight, DNA and phospholipid content increased very early (by day 2 or 4) and that triglycerides increased later. These hormonal effects are not inhibited by the beta 1-antagonist propranolol. From the morphological point of view, triiodothyronine administration induced the early proliferation and maturation of adipocyte precursors (interstitial cells and preadipocytes). It is concluded that triiodothyronine administration causes a very early hyperplasia in the brown adipose tissue similar to that observed during exposure to cold by mechanisms that may not be secondary to the involvement of norepinephrine