A Low‐Protein, High‐Carbohydrate Diet Increases Fatty Acid Uptake and Reduces Norepinephrine‐Induced Lipolysis in Rat Retroperitoneal White Adipose Tissue

Abstract

A low-protein, high-carbohydrate (LPHC) diet for 15 days increased the lipid content in the carcass and adipose tissues of rats. The aim of this work was to investigate the mechanisms of this lipid increase in the retroperitoneal white adipose tissue (RWAT) of these animals. The LPHC diet induced an approximately two- and tenfold increase in serum corticosterone and TNF-α, respectively. The rate of de novo fatty acid (FA) synthesis in vivo was reduced (50%) in LPHC rats, and the lipoprotein lipase activity increased (100%). In addition, glycerokinase activity increased (60%), and the phosphoenolpyruvate carboxykinase content decreased (27%). Basal [U-¹⁴C]-glucose incorporation into glycerol-triacylglycerol did not differ between the groups; however, in the presence of insulin, [U-¹⁴C]-glucose incorporation increased by 124% in adipocytes from only control rats. The reductions in IRS1 and AKT content as well as AKT phosphorylation in the RWAT from LPHC rats and the absence of an insulin response suggest that these adipocytes have reduced insulin sensitivity. The increase in NE turnover by 45% and the lack of a lipolytic response to NE in adipocytes from LPHC rats imply catecholamine resistance. The data reveal that the increase in fat storage in the RWAT of LPHC rats results from an increase in FA uptake from circulating lipoproteins and glycerol phosphorylation, which is accompanied by an impaired lipolysis that is activated by NE.

Higher insulin sensitivity in EDL muscle of rats fed a low-protein, high-carbohydrate diet inhibits the caspase-3 and ubiquitin-proteasome proteolytic systems but does not increase protein synthesis

“…Thus, our results suggest that despite the changes in the circulating levels of hormones and proinflammatory cytokines in LPHC rats, which strongly influenced the carbohydrate and lipid metabolism in the liver [54] and adipose tissues that were already reported in other studies [15,16,55], these factors are not the main determinants of protein metabolism in the EDL muscle.…”

“…As we previously noted, LPHC rats showed an increase in the circulating levels of corticosterone, TNF-α [16] and leptin [13] (Table S2; inhibiting eukaryotic transcription factor 2B-dependent translation (eIF2B) [48].…”

“…The data were previously published by Aparecida de França et al [13], Buzelle et al [15] and Dos Santos et al [16]. [14].…”

“…-dependent proteases, caspase-3 and the ubiquitin-proteasome proteolytic system [16]. The specificity in protein breakdown by this last proteolytic system is dependent on the content of ubiquitin ligase enzymes (E3s).…”

“…Moreover, LPHC rats showed a reduction in the body mass with a higher energetic gain as a consequence of an increase in the body lipid content and a reduction in the water and protein contents [13] (data are shown in Table S1 of the supplementary material). Additionally, the LPHC diet promotes an increase in serum epinephrine and norepinephrine levels, and 10 times higher levels of tumor necrosis factor alpha (TNF-α) and 100% higher levels of corticosterone and leptin [13,15,16]; thus, the LPHC diet seems to promote a highly catabolic environment (data are shown in Table S2 of the supplementary material). A previous study also showed a reduction in the mass of different skeletal muscles in LPHC rats compared with C rats [13].…”