The role of the tryptophan-nicotinamide pathway in a model of severe malnutrition induced liver dysfunction

Hu, Guanlan; Ling, Catriona; Chi, Lijun; Furse, Samuel; Koulman, Albert; Swann, Jonathan R.; Thind, Mehakpreet; Lee, Dorothy; Calon, Marjolein; Versloot, Christian J.; Bakker, Barbara M.; Gonzales, Gerard Bryan; Kim, Peter; Bandsma, Robert

doi:10.21203/rs.3.rs-104804/v1

Cited by 2 publications

(2 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that severe acute malnutrition affects glucose homeostasis in infants (4,36), a feature that persists later in life (37,38). Furthermore, studies in rodents have shown that post-weaning PEM induces hepatic alterations, such as steatosis and impaired hepatic mitochondrial turnover (39)(40)(41). Interestingly, two independent studies using a high-fat diet (58% kcal from fat) after LPD have shown that PEM after weaning does not potentiate fat accumulation, hepatic steatosis and insulin resistance in adult young mice (39,42).…”

Section: Discussionmentioning

confidence: 99%

Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition

Thoumas,

Cavaroc,

Sery

et al. 2024

Preprint

View full text Add to dashboard Cite

BackgroundThe highest rate of growth in mammals occurs in early life, particularly after weaning. Growth is conditioned by the nutritional status. Indeed, restriction of dietary protein in early life leads to wasting and/or stunting.ObjectiveHere, we developed a mouse model of juvenile protein malnutrition triggering stunting and studied the physiological effects of refeeding using various diets and interventions.MethodsIn a first intervention, we refed the mice with an optimal diet (breeding diet, rich in protein and fiber). We then treated the mice during the refeeding phase withLactiplantibacillus plantarumWJL (LpWJL), a previously described bacterial strain that has the ability to stimulate growth via the somatotropic axis in early life upon chronic malnutrition. Finally, we established a model of suboptimal refeeding, upon which the mice were given a western diet (33% kcal from fat; 17% kcal from protein) or an isocaloric modified western diet low in proteins (33% kcal from fat; 8% kcal from protein) after juvenile protein malnutrition.ResultsWe found that, in females, optimal growth was restored by control diet refeeding. In males, control diet refeeding after a five-week protein restriction was not enough to catch up growth retardation. No supplementary beneficial effect was found associated to the microbial intervention in this context. Surprisingly, our results showed that, in males, suboptimal refeeding with a diet rich in fat but low in protein was sufficient to buffer the deleterious effects of protein restriction on growth. However, this macroscopic benefit was associated to metabolic alteration. While LpWJLtreatment had no effect on growth per se, we found that bacterial treatment further impaired glycemic control upon suboptimal refeeding.ConclusionsOverall, we describe a novel model of juvenile protein energy malnutrition, where growth can be caught up by suboptimal refeeding.

show abstract

Section: Discussionmentioning

confidence: 99%

Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition

Thoumas,

Cavaroc,

Sery

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…It is however worth noting that liver steatosis is not a common observation among children with congenital intestinal lymphangiectasia, a disease associated with lymphatic damage 56 . Hepatic lipid accumulation in animal models of SM has so far been proposed to be related to mitochondrial dysfunction, peroxisomal damage 57, 58 or choline deficiency 59 . However, in these animal studies, rodents were fed low-protein diets which did not induce oedema.…”

Section: Discussionmentioning

confidence: 99%

Albumin-dependent and independent mechanisms in the syndrome of kwashiorkor

Gichuki

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

The syndrome of kwashiorkor is a striking phenotype of childhood severe malnutrition (SM) comprising oedema, fatty liver, and skin and hair changes. Despite high fatality, the aetiology and pathophysiology of kwashiorkor remain enigmatic, including the role of serum albumin on oedema development. Here, we demonstrate that serum albumin is associated with the presence and severity of oedema among severely malnourished children. Further, in two independent cohorts of children in Malawi and Kenya, we show albumin-independent mechanisms are associated with oedema in SM, including oxidative stress and extracellular matrix (ECM) remodelling. Plasma concentrations of ECM-related proteins: lumican, podoplanin, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) and matrix metalloproteinase (MMP)2 were associated with kwashiorkor. We therefore conclude that the pathophysiology of kwashiorkor has both albumin-dependent and independent mechanisms. We discuss the ways in which albumin-independent mechanisms may explain the clinical features observed in kwashiorkor.

show abstract

The role of the tryptophan-nicotinamide pathway in a model of severe malnutrition induced liver dysfunction

Cited by 2 publications

References 67 publications

Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition

Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition

Albumin-dependent and independent mechanisms in the syndrome of kwashiorkor

Contact Info

Product

Resources

About