Gender-Associated Impact of Early Leucine Supplementation on Adult Predisposition to Obesity in Rats

Abstract

Early nutrition plays an important role in development and may constitute a relevant contributor to the onset of obesity in adulthood. The aim of this study was to evaluate the long-term impact of maternal leucine (Leu) supplementation during lactation on progeny in rats. A chow diet, supplemented with 2% Leu, was supplied during lactation (21 days) and, from weaning onwards, was replaced by a standard chow diet. Then, at adulthood (6 months of age), this was replaced with hypercaloric diets (either with high-fat (HF) or high-carbohydrate (HC) content), for two months, to induce obesity. Female offspring from Leu-supplemented dams showed higher increases in body weight and in body fat (62%) than their respective controls; whereas males were somehow protected (15% less fat than the corresponding controls). This profile in Leu-females was associated with altered neuronal architecture at the paraventricular nucleus (PVN), involving neuropeptide Y (NPY) fibers and impaired expression of neuropeptides and factors of the mTOR signaling pathway in the hypothalamus. Interestingly, leptin and adiponectin expression in adipose tissue at weaning and at the time before the onset of obesity could be defined as early biomarkers of metabolic disturbance, predisposing towards adult obesity under the appropriate environment.

Branched Chain Amino Acids: Beyond Nutrition Metabolism

“…However, insulin may be needed for the Leu-induced in vivo stimulation of protein synthesis in skeletal muscles [ 49 ]. Apart from skeletal muscle, Leu also enhances protein synthesis in other tissues such as adipose tissue [ 50 ]. Ile or Val alone has no effectiveness as a nutrient regulator of protein synthesis in skeletal muscles [ 48 ].…”

The Association Between Leucine and Diabetic Nephropathy (DN) in Different Gender: A Cross-Sectional Study in Chinese Patients with Type 2 Diabetes

“…This is a possible speculation why leucine influence insulin secretion and then further affect the risk of DN. In other studies, it was found that the supplement of lacto-leucine during lactation take the change of insulin levels in the offspring which were affected by gender (28). This difference may be caused by that the activation of the mTOR pathway and the ribosomal kinase S6K1 showed a higher expression in female (39,40).…”

“…A study found that the supplement of leucine in diet can active the AMPK (26), which was considered as a newly identified regulator of renal hypertrophy in diabetes (26,27). Higher plasma leucine has been found to reverse the disorder of tricarboxylic acid (TCA) cycle metabolism and carnitine metabolic disorders in mice with DN (28,29). Hyperlipidemia is also a common cause of DN, and the supplementation of leucine in animal tests can reduce blood lipid (27).…”

“…As an essential amino acid, leucine has only dietary sources (28). Noticeable, protein are often restricted in diabetic patients which possibly cause a deficiency of leucine for patient (1).…”

Serum and Muscle 1H NMR-Based Metabolomics Profiles Reveal Metabolic Changes Influenced by a Maternal Leucine-Rich Diet in Tumor-Bearing Adult Offspring Rats

“…Leucine administration in premating rat dams has been explored to show its relation to improving the litter birth weight, as well as the improvement of the dams’ immune function and antioxidative capability [ 13 ]. In addition, concerning a possible leucine influence on insulin and glucose homeostasis, some studies reported that leucine supplementation during lactation in Wistar rats could improve the dams’ body composition, without compromising the offspring growth, and other studies referred to the predisposition to the obesity in adult offspring [ 14 , 15 ]. In this way, our study focused on the understanding of the metabolic responses provided by a maternal leucine-rich diet which minimized the muscle mass loss in tumor-bearing adult offspring.…”