Low-quality protein modulates inflammatory markers and the response to lipopolysaccharide insult: The case of lysine

Abstract

The relationship between non-communicable diseases (NCDs) and eating behavior has long been an area of interest. The literature largely attributes the association between NCDs and nutrition to a surplus of food and energy. However, a population observation brought to our attention a dietary factor that may explain the increase in the prevalence of NCDs among the least advantaged communities. Over the last couple of decades, the world has witnessed an increase in the prevalence of NCDs that has paralleled a major nutrition transition characterized by very high cereal intake among populations with low socioeconomic status (SES). Cereals contain low amounts of proteins, which naturally lack lysine, an essential amino acid, in adequate quantities. Lysine is a main component of the amino acid composition of both serum albumin and c-reactive protein (CRP), which concentrations were shown to change among people with low-grade inflammation, a hallmark of NCDs. Hence, it is thought that lysine deficiency might be a confounding factor explaining the association between nutrition and NCDs. In this work, we aim to study the effect of varied levels of lysine deficiency (60% and 30% deficiency) on body composition, inflammatory profile, and behavior of rats in the absence or presence of an inflammatory insult [lipopolysaccharide (LPS)]. For this purpose, two experiments were designed on five-week-old male Sprague Dawley rats to meet the objective of the work. Both experiments were identical and only differed in the level of lysine deficiency. In experiment 1, rats were randomly distributed into four groups: 1) control diet, 2) control diet+LPS, 3) 60% lysine-deficient diet, and 4) 60% lysine-deficient diet+LPS. Experiment 1 was followed by experiment 2, which held three experimental groups: 1) control diet, 2) 30% lysine-deficient diet, and 3) 30% lysine-deficient diet+LPS. Rats were only allowed their experimental diets for four weeks, during which LPS (50 µg/kg) or saline injections were administered intraperitoneally three times per week. The study showed that 60% lysine deficiency blunted growth and body compartments development, decreased albumin production, and raised hepatic c-reactive protein (CRP) expression, independently of interleukins 6 and 1β, the main precursors of CRP. Also, the 60% insufficient levels of lysine in the diet triggered hyperactivity and anxiety-like behavior. On the other hand, a marginal lysine deficiency of 30%, did not yield drastic changes in rats, suggesting dose-dependent alterations associated with the level of deficiency. LPS administration exacerbated outcomes related to body composition, metabolism, and behavior caused by 60% lysine deficiency but surprisingly did not worsen albumin and CRP expressions. This work presents evidence of varied physiological changes associated with insufficient amounts of lysine intake that can potentially increase risk factors for diseases. Thus, the increment in NCDs among the low SES populations, who heavily rely on cereals as a main source of protein may be blamed on low lysine availability in diets.