Obesity–An Update on the Basic Pathophysiology and Review of Recent Therapeutic Advances

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, antagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including intersection points to the new generation of antidiabetic drugs. We provide insight into the effectiveness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

Replacement of Palm Oil with Soybean Acid Oil in Broiler Chicken Diet: Fat Digestibility and Lipid Class Content along the Intestinal Tract

This study aimed to evaluate the replacement of palm oil (P) with increasing levels of soybean acid oil (SA), a by-product of soybean oil (S) refining, on lipid class content and fatty acid (FA) digestibility in the intestine and excreta of chickens at 11 and 35 days (d). Five experimental diets were obtained by supplementing a basal diet with 6% of P (P6), 6% of SA (SA6), 4% of P + 2% SA (P4-SA2), 2% of P + 4% of SA (P2-SA4) and 6% of S (S6). A total of 480 one-d-old female broiler chickens (Ross 308) were housed in metabolic cages (6 cages/treatment, with 16 birds/cage). Replacing P with SA improved fat absorption at 11 and 35 d (p < 0.05), but not feed AME values and saturated FA (SFA) digestibility at 11 d. As age increased, the absorption of SFA and free fatty acids (FFA) improved, and the contribution of the upper ileum to FA absorption increased (p < 0.05). At 35 d, SA6 (56% FFA) and P2-SA4 (40% FFA, 2.6 unsaturated-to-saturated FA ratio) could replace S6 without impairing fat utilization. The replacement of P with SA represents a suitable strategy to use this by-product.

Influence of Menstrual Cycle Estradiol-β-17 Fluctuations on Energy Substrate Utilization-Oxidation during Aerobic, Endurance Exercise

This study examined the effect of estradiol-β-17 across the menstrual cycle (MC) during aerobic exercise on energy substrate utilization and oxidation. Thirty-two eumenorrheic (age = 22.4 ± 3.8 y (mean ± SD)), physically active women participated in two steady-state running sessions at 65% of VO2max, one during the early follicular and one during the luteal phase of the MC. Blood samples were collected at rest before each exercise session and analyzed for Estradiol-β-17 to confirm the MC phase. Carbohydrate (CHO) utilization and oxidation values were significantly lower (p < 0.05) in the luteal (utilization: 51.6 ± 16.7%; oxidation: 1.22 ± 0.56 g/min; effect size (ES) = 0.45, 0.27) than follicular phase (utilization: 58.2 ± 15.1%; oxidation: 1.38 ± 0.60 g/min) exercise sessions. Conversely, fat utilization and oxidation values were significantly (p < 0.05) higher in the luteal (utilization: 48.4 ± 16.7%; oxidation: 0.49 ± 0.19 g/min; ES = 0.45,0.28) than follicular phase (utilization: 41.8 ± 15.1%; oxidation: 0.41 ± 0.14 g/min). Estradiol-β-17 concentrations were significantly (p < 0.01) greater during the luteal (518.5 ± 285.4 pmol/L; ES = 0.75) than follicular phase (243.8 ± 143.2 pmol/L). Results suggest a greater use of fat and reduced amount of CHO usage during the luteal versus follicular phase, directly related to the change in resting estradiol-β-17. Future research should investigate the role these changes may play in female athletic performance.

Effects of p-Synephrine during Exercise: A Brief Narrative Review

The p-synephrine is the principal phytochemical found in bitter orange (Citrus aurantium). This substance is widely included in dietary supplements for weight loss/body fat reduction due to its potential benefits of increasing fat oxidation. For years, p-synephrine-containing dietary supplements have been marketed without proper knowledge of their true effectiveness to enhance fat utilization, especially when combined with exercise. However, the effects of p-synephrine on fat oxidation during exercise have been investigated in the last few years. The aim of the current discussion is to summarize the evidence on the effects of p-synephrine intake on fat oxidation and performance during exercise. Previous investigations have demonstrated that the acute intake of p-synephrine does not modify running sprint performance, jumping capacity, or aerobic capacity. However, the acute intake of p-synephrine, in a dose of 2–3 mg/kg of body mass, has been effective to enhance the rate of fat oxidation during incremental and continuous exercise. This effect has been observed in a range of exercise workloads between 30% and 80% of peak oxygen uptake (VO2peak). The p-synephrine has the ability to increase the maximal rate of fat oxidation during exercise of increasing intensity without affecting the workload at which maximal fat oxidation is obtained (Fatmax). The effect of p-synephrine on fat oxidation is normally accompanied by a concomitant reduction of carbohydrate utilization during exercise, without modifying the energy expended during exercise. The shifting in substrate oxidation is obtained without any effect on heart rate during exercise and the prevalence of adverse effects is negligible. Thus, the acute use of p-synephrine, or p-synephrine-containing products, might offer some benefits for those individuals seeking higher fat utilization during exercise at low to moderate intensities. However, more research is still necessary to determine if the effect of p-synephrine on fat oxidation during exercise is maintained with chronic ingestion, in order to ascertain the utility of this substance in conjunction with exercise programs to produce an effective body fat/weight loss reduction.

Bilirubin Nanoparticles Reduce Diet-Induced Hepatic Steatosis, Improve Fat Utilization, and Increase Plasma β-Hydroxybutyrate

The inverse relationship of plasma bilirubin levels with liver fat accumulation has prompted the possibility of bilirubin as a therapeutic for non-alcoholic fatty liver disease. Here, we used diet-induced obese mice with non-alcoholic fatty liver disease treated with pegylated bilirubin (bilirubin nanoparticles) or vehicle control to determine the impact on hepatic lipid accumulation. The bilirubin nanoparticles significantly reduced hepatic fat, triglyceride accumulation, de novo lipogenesis, and serum levels of liver dysfunction marker aspartate transaminase and ApoB100 containing very-low-density lipoprotein. The bilirubin nanoparticles improved liver function and activated the hepatic β-oxidation pathway by increasing PPARα and acyl-coenzyme A oxidase 1. The bilirubin nanoparticles also significantly elevated plasma levels of the ketone β-hydroxybutyrate and lowered liver fat accumulation. This study demonstrates that bilirubin nanoparticles induce hepatic fat utilization, raise plasma ketones, and reduce hepatic steatosis, opening new therapeutic avenues for NAFLD.

Dimethylglycine Supplementation in Reduced Energy Broilers’ Diets Restores Performance by Improving Nutrient Digestibility

Reducing the energy content of broiler diets could lead to the formulation of diets with reduced production cost. Dimethylgycine (DMG) has been used as a dietary supplement to enhance dietary fat utilization in poultry. The objective of the present study was to investigate the effects of DMG supplementation in reduced energy diets on performance and nutrient digestibility in broiler chickens. Four hundred and eighty day-old broilers were randomly allocated to three dietary treatments: a standard energy diet (PC treatment), a reduced energy diet by 66 kcal/kg (NC treatment) and the reduced energy diet supplemented with 500 mg/kg of DMG (DMG treatment). Fat digestibility was significantly higher in DMG group, compared to PC and NC groups. Intestines and gizzard lesion scores were found to be lower in the DMG group compared to PC. DMG supplementation resulted in lower jejunum pH and ileum viscosity in broilers. Overall, the present study showed that DMG supplementation in reduced energy broiler diets restored growth performance to the levels obtained with a standard diet. This result was probably mediated by the positive effects on the gastrointestinal function of the broilers after DMG supplementation, as evidenced by the improved nutrient digestibility, the reduced gross lesion scores and the lower values in intestinal pH and viscosity.

Genetic Analysis of Peroxisomal Genes Required for Longevity in a Yeast Model of Citrin Deficiency

Citrin is a liver-specific mitochondrial aspartate–glutamate carrier encoded by SLC25A13. Citrin deficiency caused by SLC25A13 mutation results in carbohydrate toxicity, citrullinemia type II, and fatty liver diseases, the mechanisms of some of which remain unknown. Citrin shows a functional homolog in yeast aspartate-glutamate carrier (Agc1p) and agc1Δ yeasts are used as a model organism of citrin deficiency. Here, we found that agc1Δ yeasts decreased fat utilization, impaired NADH balance in peroxisomes, and decreased chronological lifespan. The activation of GPD1-mediated NAD+ regeneration in peroxisomes by GPD1 over-expression or activation of the malate–oxaloacetate NADH peroxisomal shuttle, by increasing flux in this NADH shuttle and over-expression of MDH3, resulted in lifespan extension of agc1Δ yeasts. In addition, over-expression of PEX34 restored longevity of agc1Δ yeasts as well as wild-type cells. The effect of PEX34-mediated longevity required the presence of the GPD1-mediated NADH peroxisomal shuttle, which was independent of the presence of the peroxisomal malate–oxaloacetate NADH shuttle and PEX34-induced peroxisome proliferation. These data confirm that impaired NAD+ regeneration in peroxisomes is a key defect in the yeast model of citrin deficiency, and enhancing peroxisome function or inducing NAD+ regeneration in peroxisomes is suggested for further study in patients’ hepatocytes.