In Vitro TNF‐α‐ and Noradrenaline‐Stimulated Lipolysis is Impaired in Adipocytes from Growing Rats Fed a Low‐Protein, High‐Carbohydrate Diet

Abstract

The aim of this study was to investigate tumor necrosis factor alpha (TNF-α)- and noradrenaline (NE)-stimulated lipolysis in retroperitoneal (RWAT) and epididymal (EAT) white adipose tissue as a means of understanding how low-protein, high-carbohydrate (LPHC) diet-fed rats maintain their lipid storage in a catabolic environment (marked by increases in serum TNF-α and corticosterone and sympathetic flux to RWAT and EAT), as previously observed. Adipocytes or tissues from the RWAT and EAT of rats fed an LPHC diet and rats fed a control (C) diet for 15 days were used in the experiments. The adipocytes from both tissues of the LPHC rats exhibited lower TNF-α- stimulated lipolysis compared to adipocytes from the C rats. The intracellular lipolytic agents IBMX, DBcAMPc and FSK increased lipolysis in both tissues from rats fed the C and LPHC diets compared to basal lipolysis; however, the effect was approximately 2.5-fold lower in adipocytes from LPHC rats. The LPHC diet induced a marked reduction in the β3 and α2-AR, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) content in RWAT and EAT. The LPHC diet did not affect TNF-α receptor 1 content but did induce a reduction in ERK p44/42 in both tissues. The present work indicates that RWAT and EAT from LPHC rats have an impairment in the lipolysis signaling pathway activated by NE and TNF-α, and this impairment explains the reduced response to these lipolytic stimuli, which may be fundamental to the maintenance of lipid storage in LPHC rats.

A low-protein, high-carbohydrate diet increases browning in perirenal adipose tissue but not in inguinal adipose tissue

“…The increase in ATGL and the phospho-AMPK/AMPK ratio in the ingWAT of LPHC diet-fed rats suggested increased lipolysis in the tissue, although no changes were observed in HSL level. These enzymes act sequentially; although ATGL has a high affinity for TG, HSL has a high affinity for diacylglycerol (DAG) [16]. Studies have shown that the activity of ATGL is increased following phosphorylation at Ser406 by AMPK [45] and that depletion of AMPK promotes a reduction in the phosphorylation and activity of ATGL [46].…”

“…Male Wistar rats weighing approximately 100 g (30 to 32 d old) were randomized into either the C group or the LPHC group. Rats in the C group were fed a diet containing 17% protein, 63% carbohydrates, and 7% lipids [25], and those in the LPHC group were fed a diet containing 6% protein, 74% carbohydrates, and 7% lipids for 15 d. The diets were isocaloric (16.3 kJ$g -1 ), with the energy difference from the reduction in dietary protein compensated for by increasing the carbohydrate content [13][14][15][16][17][18][19][20][21][22][23]25] (Table 1). The rats were individually housed in metabolic cages in an environmentally controlled room (lights on from 0600 to 1800; temperature 22 AE 1 C).…”

“…We have been steadily focusing on the effects of administering a low-protein, high-carbohydrate (LPHC) diet to rats, introduced during the early phase of life [13][14][15][16][17][18][19][20][21][22] because children in occidental societies are often fed diets with these characteristics, introduced soon after weaning [23]. Fifteen days after introducing this diet, alterations in the energy balance occur, along with increased food intake and energy gain; these changes increase the amount of body lipids [13].…”

“…Additionally, the LPHC diet increases energy expenditure by increasing thermogenesis in the interscapular brown adipose tissue (iBAT), enhancing UCP1 content, and resulting in a higher response to adrenaline stimulation; this attenuates the energetic gains in these animals as they ingest 18% more calories than rats fed a control (C) diet [13]. Elucidation of major changes in the hormonal profiles and specific responses from these tissues have improved the understanding of the mechanisms involved in thermogenesis in iBAT and other alterations and processes in the adipose tissues, liver, and muscles of these animals [13][14][15][16][17][18][19][20][21][22].…”

A Low‐Protein, High‐Carbohydrate Diet Stimulates Thermogenesis in the Brown Adipose Tissue of Rats via ATF‐2

“…Our laboratory has investigated the effects of a low protein, high-carbohydrate (LPHC) diet in rats [22][23][24][25][26][27][28][29] because the nutrition of children, after weaning, across the Western world is rich in carbohydrates and poor in protein content [30,31]. The administration of this diet to young rats (soon after weaning) promotes an increase in their food and calorie intake.…”