Caloric restriction, among other behavioral interventions, has demonstrated benefits on improving... more Caloric restriction, among other behavioral interventions, has demonstrated benefits on improving glycemic control in obesity-associated diabetic subjects. However, an acute and severe intervention without proper maintenance could reverse the initial benefits, with additional metabolic derangements. To assess the effects of an acute caloric restriction in a metabolic syndrome model, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without a 10-day body mass (BM) recovery period, along with their respective ad libitum controls. An oral glucose tolerance test (oGTT) was performed after CR and BM recovery. Both strains had higher rates of mass gain during recovery vs. ad lib controls; however, the regain was partial (ca. 50% of ad lib controls) over the measurement period. Retroperitoneal and epididymal adipose masses decreased 30% (8.8 g, P < 0.001) in OLETF; however, this loss only accounted for 11.5% of the total BM loss. CR decreased blood glucose AUC 16% in LETO and 19% in OLETF, without significant decreases in insulin. Following CR, hepatic expression of the gluconeogenic enzyme, PEPCK, was reduced 55% in OLETF compared to LETO, and plasma triglycerides (TG) decreased 86%. Acute CR induced improvements in glucose tolerance and TG suggestive of improvements in metabolism; however, partial recovery of BM following CR abolished the improvement in glucose tolerance. The present study highlights the importance of proper maintenance of BM after CR as only partial recovery of the lost BM reversed benefits of the initial mass loss.
Caloric restriction (CR) is the first line intervention to reduce adiposity and total body mass (... more Caloric restriction (CR) is the first line intervention to reduce adiposity and total body mass (BM) to improve insulin resistance and ameliorate metabolic derangements. However, the lost adipose mass is difficult to maintain reduced in the long term due to several factors including compensatory changes in orexigenic hormones, adipokine release, pro-inflammatory state, adipose tissue morphology, and resting metabolic rate as a consequence of the caloric deficit. Hence, most patients undergoing a BM reduction intervention ultimately regain the lost mass and too often additional adipose mass overtime, which is hypothesized to have increased deleterious effects chronically. In this mini-review we describe the effects of BM cycling (loss and regain) on insulin resistance and cardiometabolic health and factors that may predict BM regain in clinical studies. We also describe the factors that contribute to the chronic deleterious effects of BM cycling in rodent models of diet-induced obesity (DIO) and other metabolic defects. We conclude that most of the improvements in insulin resistance are observed after a profound loss in BM regardless of the diet and that BM cycling abrogates these beneficial effects. We also suggest that more BM cycling studies are needed in rodent models resembling the development of type 2 diabetes mellitus (T2DM) in humans.
Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessiv... more Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, ...
Journal of the Mexican Chemical Society, Oct 12, 2017
Poly(methacryloiloxy-o-benzoic acid), an amphiphilic weak polyelectrolyte was bound by secondary ... more Poly(methacryloiloxy-o-benzoic acid), an amphiphilic weak polyelectrolyte was bound by secondary forces to cationic drugs (propranolol. HCl and labetalol. HCl) to form water-insoluble complexes that release the bound drug only in ionic media. Compressed tablets were prepared from the polymer-drug complexes formed. The complex with propranolol suffers a fast release in simulated gastric fluid (pH 1.2), but presents a diffusion controlled release at pH 6.8 and 7.4. Moreover, the complex with labetalol (a less water soluble drug) presents controlled release at the three pH values studied. In this case, release is controlled by the erosion of the tablets. The results indicate that PMAOB is a good carrier for oral release of poorly soluble cationic drugs.
Caloric restriction, among other behavioral interventions, has demonstrated benefits on improving... more Caloric restriction, among other behavioral interventions, has demonstrated benefits on improving glycemic control in obesity-associated diabetic subjects. However, an acute and severe intervention without proper maintenance could reverse the initial benefits, with additional metabolic derangements. To assess the effects of an acute caloric restriction in a metabolic syndrome model, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without a 10-day body mass (BM) recovery period, along with their respective ad libitum controls. An oral glucose tolerance test (oGTT) was performed after CR and BM recovery. Both strains had higher rates of mass gain during recovery vs. ad lib controls; however, the regain was partial (ca. 50% of ad lib controls) over the measurement period. Retroperitoneal and epididymal adipose masses decreased 30% (8.8 g, P < 0.001) in OLETF; however, this loss only accounted for 11.5% of the total BM loss. CR decreased blood glucose AUC 16% in LETO and 19% in OLETF, without significant decreases in insulin. Following CR, hepatic expression of the gluconeogenic enzyme, PEPCK, was reduced 55% in OLETF compared to LETO, and plasma triglycerides (TG) decreased 86%. Acute CR induced improvements in glucose tolerance and TG suggestive of improvements in metabolism; however, partial recovery of BM following CR abolished the improvement in glucose tolerance. The present study highlights the importance of proper maintenance of BM after CR as only partial recovery of the lost BM reversed benefits of the initial mass loss.
Caloric restriction (CR) is the first line intervention to reduce adiposity and total body mass (... more Caloric restriction (CR) is the first line intervention to reduce adiposity and total body mass (BM) to improve insulin resistance and ameliorate metabolic derangements. However, the lost adipose mass is difficult to maintain reduced in the long term due to several factors including compensatory changes in orexigenic hormones, adipokine release, pro-inflammatory state, adipose tissue morphology, and resting metabolic rate as a consequence of the caloric deficit. Hence, most patients undergoing a BM reduction intervention ultimately regain the lost mass and too often additional adipose mass overtime, which is hypothesized to have increased deleterious effects chronically. In this mini-review we describe the effects of BM cycling (loss and regain) on insulin resistance and cardiometabolic health and factors that may predict BM regain in clinical studies. We also describe the factors that contribute to the chronic deleterious effects of BM cycling in rodent models of diet-induced obesity (DIO) and other metabolic defects. We conclude that most of the improvements in insulin resistance are observed after a profound loss in BM regardless of the diet and that BM cycling abrogates these beneficial effects. We also suggest that more BM cycling studies are needed in rodent models resembling the development of type 2 diabetes mellitus (T2DM) in humans.
Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessiv... more Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, ...
Journal of the Mexican Chemical Society, Oct 12, 2017
Poly(methacryloiloxy-o-benzoic acid), an amphiphilic weak polyelectrolyte was bound by secondary ... more Poly(methacryloiloxy-o-benzoic acid), an amphiphilic weak polyelectrolyte was bound by secondary forces to cationic drugs (propranolol. HCl and labetalol. HCl) to form water-insoluble complexes that release the bound drug only in ionic media. Compressed tablets were prepared from the polymer-drug complexes formed. The complex with propranolol suffers a fast release in simulated gastric fluid (pH 1.2), but presents a diffusion controlled release at pH 6.8 and 7.4. Moreover, the complex with labetalol (a less water soluble drug) presents controlled release at the three pH values studied. In this case, release is controlled by the erosion of the tablets. The results indicate that PMAOB is a good carrier for oral release of poorly soluble cationic drugs.
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Papers by Manuel Cornejo