A Butyrate and Niacin Supplemented Diet Reduces Corporal Fat Gain and Induces Severe Kidney Damage in a Murine Model (C57bl/6)

Abstract

Niacin and butyrate modulate cellular metabolism by several metabolic pathways. The niacin at therapeutic doses reduces blood lipid levels through the activation of its G protein receptor (GPR109), this vitamin is also a precursor of two important coenzymes involved in the cellular oxidation‐reduction processes (NAD(P)+/NAD(P)H). The consumption of butyrate in the diet produces a hypophagic effect in bovines. This effect was associated with an increase of leptin expression generating a loss of body weight. High fat diets supplemented with butyrate induce an improvement in insulin resistance in C57BL/6 mice. Butyrate also interacts with a G protein receptor (GPR 43). Both niacin and butyrate are substrates of the H+/monocarboxylate (MCT) and Na+/monocarboxylate (SMCT) transporters, these last being located in the lumen of the gastrointestinal tract and the proximal tubule of nephron. The physiological and molecular role of the receptors and transporters of the niacin and butyrate in body energy expenditure has been little studied.We used 80 C57BL/6 mice, 4 weeks old, divided into 8 groups (10 by group), were feed for 5 months with different diets with 10% kcal fat (control diets (C)) or with 45% kcal fat (high fat diet (HF)) both supplemented with 1% w/w niacin (N or HFN) or with 5% w/w butyrate (B or HFB) or with both monocarboxylates (BN; HFBN). Over the 5 month diet period were assessed weekly body weight changes with an analytical balance and monthly changes in body fat concentration with the EchoMRI ™ 4 in 1–500 small live animal body composition analyzers. The calorimetry analysis was performed with Columbus Instruments, Comprehensive Lab Animal Monitoring System: CLAMS. Several organs were extracted, including the kidneys for studies of protein and gene expression by WB and qPCR analysis respectively. The blood chemistry of the different groups was also evaluated. The renal function and physiology status of animals prior to slaughter was evaluated by the 24h urine collection in metabolic cages to evaluate various ions and metabolites.We observed that the co‐administration of butyrate and niacin prevents body weight gain. The calorimetric analysis showed that the energy expenditure in the HFBN group was higher than the HF group (P< 0.0001), similar situation was observed in the oxygen consumption (P< 0.039). The respiratory coefficient (RER) was 0.7 in HF and HFBN groups, suggesting an increase in fatty acid oxidation. In the body composition analysis the HFBN group gain a similar fat mass compared to C group with a maintained of fat free mass. The reduction of fat mass in HFBN group was significant compared with the HF group (P< 0.01). Interesting the mice groups that eat butyrate supplemented diets developed renal hyperplasia and hydronephrosis. The expressions of both SMCTs in the kidneys of BN and HFBN groups were significant reduced in contrast with C and HF groups. Also significant increment of UCP2 expression was observed in these groups.We conclude that the consumption of butyrate with niacin favors the oxidation of fatty acids and increased caloric expenditure that that modifies the expression of both SMCTs and UCP2 genes, however, as an adverse effect, butyrate diets causes a significant increase in serum creatinine and BUN and as observed in the histological analysis exist a loss of renal architecture. This effect is possibly caused by an obstruction in the renal tubules inducing a renal damage.Support or Funding InformationINCMSZ‐AI‐015 (CP) CONACYT 155700 (VR)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.