Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring

Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of “metabolic programming”. The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood

Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring

Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of “metabolic programming”. The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood

Rôle de la détection centrale des lipides dans le contrôle nerveux de la balance énergétique

Il existe, dans l’hypothalamus et dans d’autres structures cérébrales comme l’hippocampe ou le striatum, des neurones spécialisés capables de détecter les variations quotidiennes des acides gras circulants. Ces neurones participent au maintien à l’équilibre de la balance énergétique en contrôlant la prise alimentaire, la sécrétion d’insuline ou la production hépatique de glucose. Les mécanismes moléculaires relayant l’effet des acides gras impliquent des récepteurs d’acides gras comme FAT (fatty acid transporter)/CD36. Toute dérégulation de cette détection centrale des acides gras peut contribuer à la mise en place des maladies métaboliques, telles que l’obésité ou le diabète de type 2

The regulator of G-protein signaling RGS16 promotes insulin secretion and β-cell proliferation in rodent and human islets

Objective: G protein-coupled receptor (GPCR) signaling regulates insulin secretion and pancreatic β cell-proliferation. While much knowledge has been gained regarding how GPCRs are activated in β cells, less is known about the mechanisms controlling their deactivation. In many cell types, termination of GPCR signaling is controlled by the family of Regulators of G-protein Signaling (RGS). RGS proteins are expressed in most eukaryotic cells and ensure a timely return to the GPCR inactive state upon removal of the stimulus. The aims of this study were i) to determine if RGS16, the most highly enriched RGS protein in β cells, regulates insulin secretion and β-cell proliferation and, if so, ii) to elucidate the mechanisms underlying such effects. Methods: Mouse and human islets were infected with recombinant adenoviruses expressing shRNA or cDNA sequences to knock-down or overexpress RGS16, respectively. 60 h post-infection, insulin secretion and cAMP levels were measured in static incubations in the presence of glucose and various secretagogues. β-cell proliferation was measured in infected islets after 72 h in the presence of 16.7 mM glucose ± somatostatin and various inhibitors. Results: RGS16 mRNA levels are strongly up-regulated in islets of Langerhans under hyperglycemic conditions in vivo and ex vivo. RGS16 overexpression stimulated glucose-induced insulin secretion in isolated mouse and human islets while, conversely, insulin secretion was impaired following RGS16 knock-down. Insulin secretion was no longer affected by RGS16 knock-down when islets were pre-treated with pertussis toxin to inactivate Gαi/o proteins, or in the presence of a somatostatin receptor antagonist. RGS16 overexpression increased intracellular cAMP levels, and its effects were blocked by an adenylyl cyclase inhibitor. Finally, RGS16 overexpression prevented the inhibitory effect of somatostatin on insulin secretion and β-cell proliferation. Conclusions: Our results identify RGS16 as a novel regulator of β-cell function that coordinately controls insulin secretion and proliferation by limiting the tonic inhibitory signal exerted by δ-cell-derived somatostatin in islets. Author Video: Author Video Watch what authors say about their articles Keywords: G protein-coupled receptor, Regulator of G protein signaling, Pancreatic beta-cell, Insulin secretion, Proliferatio

Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food intake in rats.

Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/- heparin (IL, IL(H), respectively) or saline/heparin (SH) were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1) Rats previously injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA; 2) Etomoxir (CPT1 inhibitor) or saline co-infused with IL(H)/S(H); and 3) Triacsin C (acylCoA synthase inhibitor) or saline co-infused with IL(H)/S(H). IL(H) significantly lowered food intake during refeeding compared to S(H) (p<0.001). Five hours after refeeding, etomoxir did not affect this inhibitory effect of IL(H) on food intake while VMN CD36 depletion totally prevented it. Triacsin C also prevented IL(H) effects on food intake. In conclusion, the effect of FA to inhibit food intake is dependent on VMN CD36 and acylCoA synthesis but does not required FA oxidation

Food intake measurement after 10 min infusion toward brain of S_H (open bars; control), S_H+treatment (light grey bars), IL_H (solid bars) and IL_H+treatment (dark grey bars) groups.

<p>A, B: 1 h-food intake (A) and 5 h-food intake (B) in scramble and CD36 shRNA rats infused with S_H or IL_H. C, D: 1 h-food intake (C) and 5 h-food intake (D) in S_H and IL_H groups co-infused with triacsin C (80 µM). E,F: 1 h-food intake (E) and 5 h-food intake (F) in S_H and IL_H groups co-infused with etomoxir (150 µM). Values are means ±SEM; n ≥4 rats/group. ***p<0.001, significantly different from S_H; ^§§p<0.01 significantly different from S_H+treatment. ^#p<0.05, ^##p<0.01 significantly different from IL_H.</p

Schematic representations of proteins mediating FA effect on food intake in a fatty acid sensing cell.

<p>Schematic representations of proteins mediating FA effect on food intake in a fatty acid sensing cell.</p