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It was previously reported that liver glucose metabolism in rats under caloric restriction differs from that of freely-fed rats. This study hypothesized that these changes (1) were related to the expression of hypothalamic neuropeptides involved in metabolic control, and (2) were not a residual effect of litter size. To those purposes, liver glucose metabolism and hypothalamic expression of the orexigenic neuropeptides NPY (neuropeptide Y) and AgRP (agouti gene-related peptide); and of the anorexigenic neuropeptides POMC (pro-opiomelanocortin) and CART (cocaine- and amphetamine-related transcripts) were investigated. Male Wistar rats from two different litter sizes (G6 and G12, with 6 or 12 pups, respectively) were subjected to free feeding (GL, ad libitum ), 50% caloric restriction (GR) or caloric restriction+ ad libitum refeeding (GRL) until the age of 90 days. Biometric values were lower in GR than in GL, while in GRL they were totally or partially recovered. Blood glucose variation during the pyruvate tolerance test (PTT) was small in GR. During in situ liver perfusion, total, basal, and adrenaline-stimulated liver glucose outputs were high in GR, but additional glucose output in the presence of alanine was negligible. Refeeding (GRL) yielded values close to those of GL. Litter size did not consistently influence any of these variables. The expression of transcripts of the hypothalamic neuropeptides was responsive to feeding regimen, litter size and/or their interaction and differed from G6 to G12, while the metabolic changes of the liver were qualitatively equal in both GR. Therefore, the changes in glucose metabolism in the liver of rats under caloric restriction were not determined by either litter size or hypothalamic neuropeptide expression and were linked only to the prevailing feeding regimen of the adult animal., (Copyright © 2020 Mariano, Yamada, Soares Rabassi, Rissi Sabino, Bataglini, Azevedo, Garcia and Pedrosa.)

Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.

Background: Caloric restriction since birth changes glucose metabolism by the liver in overnight-fasted rats to a fed-like pattern, in which glucose output is large but gluconeogenesis is negligible. It was investigated whether these changes could be a residual effect of the nutritional condition during lactation and what could be the mechanism of such change., Methods: Newborn Wistar rat pups were arranged in litters of 6 or 12 (G6 and G12). After weaning, the male pups were divided in: G6L and G12 L, fed freely until the age of 90 days (freely-fed groups); G6R and G12R, given 50% of the GL ingestion (food-restricted groups) until 90 days of age; G6RL and G12RL, given 50% of the GL ingestion until 60 days of age and fed freely until 90 days of age (refed groups). The experimental protocols were carried out at the age of 90 days after overnight fasting. Pairs of groups were compared through t test; other statistical comparisons were made with one-way ANOVA with Tukey post hoc text., Results: Caloric restriction was effective in decreasing body and fat weights, total cholesterol and LDL. These effects were totally or partially reversed after 30 days of refeeding (groups GRL). During liver perfusion, the high glucose output of the GRs was further enhanced by adrenaline (1 μM), but not by lactate infusion. In contrast, in groups G6L, G12 L, G6RL and G12RL glycogenolysis (basal and adrenaline-stimulated glucose output) was low and gluconeogenesis from lactate was significant. A twofold increase in liver content of PKA in group G6R suggests that liver sensitivity to glucagon and adrenaline was higher because of caloric restriction, resulting in enhanced glucose output., Conclusions: As glucose output was not affected by litter size, liver glucose metabolism in the adult rat, in contrast to other metabolic processes, is not a programmed effect of the nutritional condition during lactation. In addition, the increased expression of PKA points to a higher sensitivity of the animals under caloric restriction to glycogenolytic hormones, a relevant condition for glucose homeostasis during fasting., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)