Adipose tissue homeostasis orchestrates the oxidative, energetic, metabolic and endocrine disruption induced by binge drinking in adolescent rats

Abstract

Binge drinking (BD) is the most common alcohol consumption model for adolescents, and has recently been related to the generation of high oxidation and insulin resistance (IR). White adipose tissue (WAT) is a target organ for insulin action that regulates whole‐body metabolism by secreting adipokines. The present study aimed to analyse the oxidative, inflammatory, energetic and endocrine profile in the WAT of BD‐exposed adolescent rats, to obtain an integrative view of insulin secretion and WAT in IR progression. Two groups of male adolescent rats were used: control (n = 8) and BD (n = 8). An intermittent i.p. BD model (20% v/v) was used during 3 consecutive weeks. BD exposure led to a pancreatic oxidative imbalance, which was joint to high insulin secretion by augmenting deacetylase sirtuin‐1 (SIRT‐1) pancreatic expression and serum adipsin levels. However, BD rats had hyperglycaemia and high homeostasis model assessment of insulin resistance value (HOMA‐IR). BD exposure in WAT increased lipid oxidation, as well as decreased insulin receptor substrate 1 (IRS‐1) and AKT expression, sterol regulatory element‐binding protein 1 (SREBP1), forkhead box O3A (FOXO3a) and peroxisome proliferator‐activated receptor γ (PPARγ), and adipocyte size. BD also affected the expression of proteins related to energy balance, such as SIRT‐1 and AMP activated protein kinase (AMPK), affecting the adipokine secretion profile (increasing resistin/adiponectin ratio). BD altered the entire serum lipid profile, increasing the concentration of free fatty acids. In conclusion, BD led to an oxidative imbalance and IR process in WAT, which modified the energy balance in this tissue, decreasing the WAT lipogenic/lipolytic ratio, affecting adipokine secretion and the systemic lipid profile, and contributing to the progression of IR. Therefore, WAT is key in the generation of metabolic and endocrine disruption after BD exposure during adolescence in rats. imageKey points Adolescent rat binge drinking (BD) exposure leads to hepatic and systemic oxidative stress (OS) via reactive oxygen species generation, causing hepatic insulin resistance (IR) and altered energy metabolism. In the present study, BD exposure in adolescent rats induces OS in the pancreas, with increased insulin secretion despite hyperglycaemia, indicating a role for IR in white adipose tissue (WAT) homeostasis. In WAT, BD produces IR and an oxidative and energetic imbalance, triggering an intense lipolysis where the serum lipid profile is altered and free fatty acids are increased, consistent with liver lipid accumulation and steatosis. BD exposure heightens inflammation in WAT, elevating pro‐inflammatory and reducing anti‐inflammatory adipokines, favouring cardiovascular damage. This research provides a comprehensive view of how adolescent BD in rats impacts liver, WAT and pancreas homeostasis, posing a risk for future cardiometabolic complications in adulthood.

Selenium supplementation via modulation of selenoproteins ameliorates binge drinking-induced oxidative, energetic, metabolic, and endocrine imbalance in adolescent rats’ skeletal muscle

“…6G). In a previous recent paper, 8 we confirmed that BD exposure during adolescence led to hyperglycemia and hyperinsulinemia, which were compatible with a general IR process.…”

“…1 Therefore, addictive disorders related to substances and/or behaviors typically begin during adolescence or early adulthood. 2 Besides, this age group is especially susceptible to the toxicity of ethanol (EtOH); 3–8 in this context, binge drinking (BD) is a pattern of acute EtOH consumption that has lately been prominently favored by teenagers, 9,10 consisting of reaching a blood alcohol concentration of 0.08% or higher within 2 hours. 11 The harmfulness of BD resides in its pronounced pro-oxidant effect on DNA, proteins and lipids, as it greatly induces the hepatic activity of cytochrome P450 2E1 (CYP2E1), much more than chronic alcoholism.…”

“…3,5,18,19 Moreover, in the three principal target organs for insulin action, the liver, skeletal muscle (SKM) and adipose tissue, adolescent rats after BD exposure exhibited dysregulation of two crucial cellular energy sensors, AMP activated protein kinase (AMPK) and NAD + -dependent deacetylase sirtuin 1 (SIRT-1); this can be related to depletion in the expression of the insulin receptor substrate 1 (IRS-1), which was also found. 5,7,8 This situation predisposes adolescents to the development of insulin resistance (IR), 20,21 which is a factor in metabolic syndrome, that has lately become a highly prevalent disease in adolescents. 22,23…”

Uncovering the Role of Selenite and Selenium Nanoparticles (SeNPs) in Adolescent Rat Adipose Tissue beyond Oxidative Balance: Transcriptomic Analysis

“…The activity of superoxide dismutase (SOD), catalase (CAT), and GPx was assayed in WAT homogenates following the methods previously described [ 29 ]. GPx activity (mU/mg protein) was determined by measuring the decrease in absorbance at 340 nm caused by nicotinamide adenine dinucleotide phosphate (NADPH) oxidation [ 30 ].…”