Modulation of hypothalamic AMPK and hypothalamic neuropeptides in the control of eating behavior: A systematic review.

Eating behavior is regulated by central and peripheral signals, which interact to modulate the response to nutrient intake. Central control is mediated by the hypothalamus through neuropeptides that activate the orexigenic and anorexigenic pathways. Energy homeostasis depends on the efficiency of these regulatory mechanisms. This neuroendocrine regulation of hunger and appetite can be modulated by nutritional sensors such as adenosine monophosphate-activated protein kinase (AMPK). Thus, this systematic review discusses the literature on correlations between AMPK and hypothalamic neuropeptides regarding control of eating behavior. Lilacs, PubMed/Medline, ScienceDirect, and Web of Science were searched for articles published from 2009 to 2021 containing combinations of the following descriptors: "eating behavior," "hypothalamus," "neuropeptide," and "AMPK." Of the 1330 articles found initially, 27 were selected after application of the inclusion and exclusion criteria. Of the selected articles, 15 reported decreased AMPK activity, due to interventions using angiotensin II infusion, fructose, glucose, cholecystokinin, leptin, or lipopolysaccharide (LPS) injection; dietary control through a low-protein diet or a high-fat diet (60 % fat); induction of hyperthyroidism; or injection of AMPK inhibitors. Seven studies showed a decrease in neuropeptide Y (NPY) through CV4 AICAR administration; fructose, glucose, leptin, or angiotensin II injections; or infusion of LPS from Escherichia coli and liver kinase B1 (LKB1) overexpression. Eleven studies reported a decrease in food consumption due to a decrease in AMPK activity and/or hypothalamic neuropeptides such as NPY. The results indicate that there is a relationship between AMPK and the control of eating behavior: a decrease in AMPK activity due to a dietary or non-dietary stimulus is associated with a consequent decrease in food intake. Furthermore, AMPK activity can be modulated by glucose, thyroid hormones, estradiol, leptin, and ghrelin.

Perinatal and post-weaning exposure to an obesogenic diet promotes greater expression of nuclear factor-κB and tumor necrosis factor-α in white adipose tissue and hypothalamus of adult rats.

Aim: To analyze the effects of exposure to a high-fat diet during the perinatal period and after weaning on white adipose tissue accumulation and gene expression of TNF- α and NF- κB.Method: Wistar female rats were fed with high-fat (H) or control (C) diet during pregnancy and lactation. The offspring were allocated into four groups: Control Control (CC), offspring of mothers GC, fed a control diet after weaning; Control High-fat (CH), offspring of mothers GC, fed a hight-fat diet after weaning; High-fat Control (HC), offspring of mothers GH, fed with control diet after weaning; and High-fat High-fat (HH), offspring of mothers GH, fed a H diet after weaning.Results: HH and HC groups showed increased body weight compared to CC group and increases in caloric intake, larger amount of white adipose tissue and adipocyte size compared to CC and CH groups. The HH and CH groups showed higher NF-kB expression in white adipose tissue compared to the CC and HC groups, and the HH group also showed higher TNF- α expression. In the hypothalamus, the HH and HC groups exhibited higher TNF- α expression compared to the CC and CH groups.Conclusion: Perinatal and post-weaning exposure to the high-fat diet increases the amount of white adipose tissue, adipocyte size, and expression of the inflammatory genes TNF-α and NF-kB.

Early life stress induced by maternal separation during lactation alters the eating behavior and serotonin system in middle-aged rat female offspring.

Stressful events occurring during early life have been related to behavioral and neurochemical disturbances. Maternal separation during the first two weeks of life is a traumatic event that strongly affects the feeding behavior and serotonergic system of the progeny in adulthood. As this system modulates the feeding behavior, the present study aimed at investigating the effects of maternal separation-induced stress on both the feeding behavior and serotonergic system of the middle-aged female rats by manipulating this system using fluoxetine, a selective serotonin transporter inhibitor. Lactating Wistar rats were separated from their litters from postnatal day 2 (PND 2) to PND 14 for 3 h in the dark phase of the circadian cycle. The maternally separated (MS) and control (C) groups were distinguished from each other based on the incidence or absence of maternal separation (early life stress). All the analyses were done on the female offspring from one-year of age. Maternal separation anticipated the satiety point in these females. This anticipation was linked to lower food intake, meal duration and meal size. These results mirrored the effects of fluoxetine in the control animals. Furthermore, maternal separation was associated with 5ht1b serotonin receptor hyperexpression in the hypothalamus. These findings demonstrate that maternal separation has long-lasting effects on the eating behavior and serotonergic system and that this system could be responsible for mediating these behavioral outcomes.

Neonatal fluoxetine exposure modulates serotonergic neurotransmission and disturb inhibitory action of serotonin on food intake.

The neurotransmitter serotonin (5-HT) acts as an important regulator of the critical neurodevelopmental processes and thus alterations in 5-HT signaling early promotes permanent structural and functional changes in brain. The selective serotonin reuptake inhibitors (SSRIs), as fluoxetine and citalopram, blocking serotonin transporter (SERT) at the presynaptic neuron, which regulates extracellular 5-HT levels. Evidence suggests that the exposure to SSRIs in the neurodevelopmental period may alters 5-HT signaling sensitivity on food intake control. The aim of the present study was to evaluate the effects of neonatal exposure to fluoxetine on molecular and cellular components of the serotonergic system and food intake control in young animals. Methods: The animals were divided according to experimental manipulation, Fluoxetine Group (FG): male pups received application of fluoxetine (10 mg/kg, 10 µL/g) and Saline Group (SG): male pups received saline application (0.9% NaCl, 10 µL/g), both throughout lactation (PND1-PND21). They evaluated body weight, food intake, SERT gene and protein expression, serotonin content in the hypothalamus. The neonatal exposure to fluoxetine promoted reduction in body weight, disturb the serotonin hypophagic response, and increase the serotonin and SERT hypothalamic in young animals. We conclude that the changes of components of the serotonergic system by neonatal exposure to fluoxetine may be responsible for disturb the inhibitory action of serotonin on food intake.

Supplementation-Dependent Effects of Vegetable Oils with Varying Fatty Acid Compositions on Anthropometric and Biochemical Parameters in Obese Women.

Fatty acid (FA) composition is a determinant of the physiological effects of dietary oils. This study investigated the effects of vegetable oil supplementation with different FA compositions on anthropometric and biochemical parameters in obese women on a hypocaloric diet with lifestyle modifications. Seventy-five women (body mass index, BMI, 30⁻39.9kg/m²) were randomized based on 8-week oil supplementation into four experimental groups: the coconut oil group (CoG, n = 18), the safflower oil group (SafG, n = 19), the chia oil group (ChG, n = 19), and the soybean oil placebo group (PG, n = 19). Pre- and post-supplementation weight, anthropometric parameters, and body fat (%BF), and lean mass percentages (%LM) were evaluated, along with biochemical parameters related to lipid and glycidemic profiles. In the anthropometric evaluation, the CoG showed greater weight loss (Δ% = -8.54 ± 2.38), and reduced BMI (absolute variation, Δabs = -2.86 ± 0.79), waist circumference (Δabs = -6.61 ± 0.85), waist-to-height ratio (Δabs = -0.041 ± 0.006), conicity index (Δabs = -0.03 ± 0.016), and %BF (Δabs = -2.78 ± 0.46), but increased %LM (Δabs = 2.61 ± 1.40) (p < 0.001). Moreover, the CoG showed a higher reduction in biochemical parameters of glycemia (Δabs = -24.71 ± 8.13) and glycated hemoglobin (Δabs = -0.86 ± 0.28) (p < 0.001). The ChG showed a higher reduction in cholesterol (Δabs = -45.36 ± 0.94), low-density lipoprotein cholesterol (LDLc; Δabs = -42.53 ± 22.65), and triglycerides (Δabs = -49.74 ± 26.3), but an increase in high-density lipoprotein cholesterol (HDLc; abs = 3.73 ± 1.24, p = 0.007). Coconut oil had a more pronounced effect on abdominal adiposity and glycidic profile, whereas chia oil had a higher effect on improving the lipid profile. Indeed, supplementation with different fatty acid compositions resulted in specific responses.

Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats.

BACKGROUND: Serotonin (5-HT) is involved in nervous system ontogenesis, and is important for neurotransmission and behavior modulation after the developmental stage. Alterations in 5-HT levels during the early period of life may signal to feeding behavior and hypothalamic genic expression changes in adulthood. OBJECTIVES: Investigate the effects of hypercaloric diet in adult rats submitted to neonatal serotonin reuptake inhibition on food intake, fat pad mass, plasmatic triglycerides/cholesterol and gene expression of hypothalamic peptides (POMC, NPY) and serotonin receptors (5-HT1B, 5-HT2C). METHODS: In each litter, 8 pups were divided into two groups: control (C) and fluoxetine (F). From the 1(st) to the 21(st) postnatal day, C pups received sterile saline while F pups received fluoxetine (10mg/kg). From 180 to 215 days, a group of rats from C and F groups were fed hypercaloric diet (CH and FH, 421.4Kcal/100 g) while the rest of animals from C and F groups fed chow diet (CC and FC). RESULTS: The use of hypercaloric diet was associated with lower accumulation of white adipose tissue in adult rats subjected to neonatal serotonin reuptake inhibition. Adult rats of group FC showed decreased 5-HT2C and neuropeptide Y mRNA expression compared with control chow diet group (CC). After chronic use of a hypercaloric diet, the expression of 5-HT2C was higher in the FH group than the FC group and neuropeptide Y expression decreased in FH related to FC. CONCLUSIONS: These findings suggest that neonatal serotonin reuptake inhibition is associated with better adaptation to hypercaloric diet in adult rats.