Maternal dietary fatty acid composition and content prior to and during pregnancy and lactation influences serum profile, liver phenotype and hepatic miRNA expression in young male and female offspring.

This study aimed to investigate whether modifying the pre-gestational lipid content could mitigate metabolic damage in offspring from dams exposed to a high-fat (HF) diet before conception and during pregnancy and lactation, with a focus on sex-specific outcomes. Specific effects of maternal normolipidic diets on offspring were also assessed. Female Wistar rats received control (C) or HF diets before conception. During pregnancy and lactation, females were distributed in five groups: C-C, HF-HF, HF-C, HF-saturated (HF-S) or HF-polyunsaturated n-3 group (HF-P). Saturated and PUFA n-3 diets were normolipidic. In 21-day-old offspring, corporal parameters, adiposity, serum metabolites, OGTT, liver phenotype, and miR-34a-5p hepatic expression were determined. Pre-gestational HF diet impaired glycemic response in females, independent of any change in body weight. Female and male offspring from dams continuously exposed to HF diet exhibited hyperglycemia, increased adiposity, and disrupted serum lipid profiles. Male offspring showed increased hepatic fat accumulation and miR-34a-5p expression. Shifting maternal dietary lipid content to normolipidic diets restored offspring's phenotype; however, decreased SIRT1, IRß and IRS1 expression in offspring from dams exposed to HF diet before conception suggested early indicators of glucose metabolism damage. Our findings indicated a pronounced metabolic impact on males. In conclusion, glucose tolerance impairment in females before conception disturbed intrauterine environment, influencing in offspring's phenotype. Modifying maternal dietary lipid content mitigated effects of pre-gestational HF diet exposure on young offspring. Nevertheless, decreased hepatic levels of critical insulin signaling proteins indicated that independently of the maternal diet, pre-existing HF diet-induced glucose intolerance before conception may adversely program the offspring's phenotype.

Cytogenotoxicity and inflammatory response in liver of rats exposed to different doses of cannabis nano emulsions.

Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.

Hepatic Effects of Low-Carbohydrate Diet Associated with Different Lipid Sources: Insights into Oxidative Stress, Cytotoxicity, and Epigenetic Markers in a mouse Model of Obesity.

BACKGROUND: Low-carbohydrate and high-fat diet (LCHF) models have been widely explored as alternatives for treating obesity and promoting weight loss. Their effect is attributed to the change in energy substrate that stimulates ketogenic pathways that can metabolically overload the liver. However, little has been studied about the impact of lipid sources prioritized in the LCHF diet. OBJECTIVES: This study aims to evaluate the impact of different fat sources in the LCHF diet on markers of liver injury, oxidative stress, and epigenetics in obesity. METHODS: Adult male mice were initially induced to obesity by a high-fat and high-sugar diet for 10 wk. Subsequently, they underwent a weight-loss treatment intervention involving an LCHF diet with various sources of fats, including saturated, omega-3 (ω-3) (n-3), omega-6 (ω-6) (n-6), and omega-9 (ω-9) (n-9). At the end of the treatment, markers of liver injury, oxidative stress, and epigenetics were evaluated. RESULTS: The LCHF diet was effective in inducing weight loss. However, unsaturated lipid sources (omegas) exhibited superior outcomes. Specifically, the ω-9 group displayed diminished oxidative stress concentrations and decreased markers of liver injury. The ω-3 group demonstrated efficacy in modulating epigenetic markers, thereby reducing oxidative stress, mutagenicity, and markers of liver injury. Correlation tests demonstrated that there was an interaction between the activity of antioxidants and epigenetic enzymes. CONCLUSIONS: Our results suggest that LCHF diets associated with ω-3 and ω-9 have the potential for weight loss and liver health recovery in obesity through antioxidant and epigenetic mechanisms.

Effect of Kinins on the Hepatic Oxidative Stress in Mice Treated with a Methionine-Choline Deficient Diet.

Non-alcoholic fatty liver is the leading cause of hepatic disease worldwide and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) due to cell injury, oxidative stress, and apoptosis. The kinins' role in the liver has been studied in experimental fibrosis, partial hepatectomy, and ischemia-reperfusion and is related to cell death and regeneration. We investigated its role in experimental NASH induced by a methionine-choline deficient diet for 4 weeks. After that, liver perfusion was performed, and bradykinin (BK) or des-Arg9-BK was infused. Cell death was evaluated by cathepsin-B and caspase-3 activity and oxidative stress by catalase (CAT), glutathione S-transferase, and superoxide dismutase (SOD) activities, as well as malondialdehyde and carbonylated proteins. In control livers, DABK increased CAT activity, which was reversed by antagonist DALBK. In the NASH group, kinins tend to decrease antioxidant activity, with SOD activity being significantly reduced by BK and DABK. Malondialdehyde levels increased in all NASH groups, but carbonylated protein did not. DABK significantly decreased cathepsin-B in the NASH group, while caspase-3 was increased by BK in control animals. Our results suggest that B1R and/or B2R activation did not induce oxidative stress but affected the antioxidant system, reducing SOD in the NASH group.

Role of carotenoids in adipose tissue through the AMPK-mediated pathway.

Diet is a critical factor in controlling adiposity and white adipose tissue (WAT) physiology. A high-fat diet (HFD) alters WAT function and affects AMP-activated protein kinase (AMPK) - a cellular sensor - dysregulating lipolysis and lipid metabolism in adipocytes. Otherwise, AMPK activation may attenuate oxidative stress and inflammation. Interest in natural therapies, such as carotenoid consumption or supplementation, is growing due to their health benefits. Carotenoids are lipophilic pigments present in vegetables and fruits, which cannot be synthesized by the human body. Interventions focused on ameliorating complications induced by a HFD indicate a positive contribution of the carotenoids to the AMPK activation. This review aims to outline the mechanism of carotenoids in the AMPK pathway in adipose tissue and their contribution in regulating adipogenesis. Different carotenoids can act as an agonist of the AMPK signaling pathway, activating upstream kinases, upregulating transcriptional factors, inducing WAT browning, and blocking adipogenesis. In addition, the improvement of some "homeostatic" factors, such as adiponectin, may mediate the AMPK activation induced by carotenoids. With these findings, we encourage clinical trials to confirm the role of carotenoids in the AMPK pathway in a long-term treatment, mainly in obesity cases.

Could parental high-fat intake program the reproductive health of male offspring? A review.

High-fat diet (HFD) intake can cause overweight and obesity and has become a global public health concern in recent years. Nutritional adversity at vulnerable windows of development can affect developing cells and their functions, including germ cells. Evidence shows that parental HFD intake prior to conception and/or during gestation and lactation could program the reproductive health of male offspring, ultimately resulting in impairment of the first as well as subsequent generations. In male offspring, adipose tissue and hypothalamic-pituitary-gonadal axis imbalance can impair the production of gonadotropins, leading to dysfunction of testosterone production and pubertal onset. The gonads can be directly impaired through oxidative stress, causing poor testosterone production and spermatogenesis; low sperm count, viability, and motility; and abnormal sperm morphology, which results in low sperm quality. Parental HFD intake could also be a risk factor for prostate hyperplasia and cancer in advanced age. It can impact the reproductive pattern of male offspring resulting in impairments in the subsequent generations. The investigation of semen quality must be extended to epidemiological and clinical studies of the male offspring of overweight and/or obese parents in order to improve the quality of human semen. This review addresses the effects of parental HFD intake on the reproductive parameters of male offspring and discusses the possible underlying mechanisms.

Proanthocyanidins in grape seeds and their role in gut microbiota-white adipose tissue axis.

Several factors can impact the gut microbiota, affecting host metabolism and immunity. It implies intestinal barrier disruption and translocation of gut microbiota metabolites to the bloodstream, such as lipopolysaccharides (LPS). LPS is an endotoxin from gram-negative gut bacteria that trigger the activation of the Toll-like receptor-4 (TLR-4) inflammatory pathway and can modulate white adipose tissue (WAT) metabolism. Dietary components, including diets rich in fiber and polyphenols, contribute to intestinal environment homeostasis. Grape seed proanthocyanidins extract (GSPE) may improve intestinal permeability and microbial diversity and increase short-chain fatty acids production. Furthermore, GSPE has been involved in LPS reduction, down-regulating the TLR-4 pathway, decreasing the WAT metainflammatory profile, and preventing adipocyte hypertrophy. Studies have pointed out strategies to promote health and control obesity by modulating the gut microbiota environment. Therefore, this review aims to summarize the potential effects of GSPE on the gut microbiota-white adipose tissue axis against obesity.

Inflammatory crosstalk between saturated fatty acids and gut microbiota-white adipose tissue axis.

PURPOSE: High-fat diets have different metabolic responses via gut dysbiosis. In this review, we discuss the complex interaction between the intake of long- and medium-chain saturated fatty acids (SFAs), gut microbiota, and white adipose tissue (WAT) dysfunction, particularly focusing on the type of fat. RESULTS: The evidence for the impact of dietary SFAs on the gut microbiota-WAT axis has been mostly derived from in vitro and animal models, but there is now also evidence emerging from human studies. Most current reports show that, in response to high long- and medium-chain SFA diets, WAT functions are altered and can be modulated from microbial metabolites in several manners; and it appears to be also modified under conditions of obesity. SFAs overconsumption can reduce bacterial content and disrupt the gut environment. Both long- and medium-chain SFAs may contribute to proinflammatory cytokines release and TLR4 cascade signaling, either by regulation of endotoxemia markers or myristoylated protein. Palmitic and stearic acids have pathological effects on the intestinal epithelium, microbes, and inflammatory and lipogenic WAT profiles. While myristic and lauric acids display somewhat controversial outcomes, from probiotic effects and contribution to weight loss to cardiometabolic alterations from WAT inflammation. CONCLUSION: Identifying an interference of distinct types of SFA in the binomial gut microbiota-WAT may elucidate essential mechanisms of metabolic endotoxemia, which may be the key to triggering obesity, innovating the therapeutic tools for this disease.

Hippocampal BDNF mediated anxiety-like behaviours induced by obesogenic diet withdrawal.

Obesogenic diets (ODs) consumption is associated with anxiety-like behaviour and negative changes in hippocampal BDNF. At the same time, interrupting OD intake, OD withdrawal (WTD), can bring health benefits, but previous studies reported the development of anxiety-like behaviours. The present work aimed to assess the relationship between anxiety-like behaviour with hippocampal BDNF in a WTD rodent model. Male Wistar rats (60d old) were fed a high-sugar/high-fat (HSHF) diet for 30d (n = 32), and half of them were transitioned to a control diet for 48 h (n = 16) afterwards. The control group (n = 16) was fed a control diet across the whole experiment. Besides increasing anxiety-like behaviours and lowering sociability, the WTD led to an increase in BDNF in the dentate gyrus and the CA1 of the hippocampus. It also decreased locomotor activity in both OF and EPM, however, they did not significantly interfere with the other behavioural parameters analysed. Western blotting analysis revealed that the increase in BDNF likely occurred in the mature forms (14 kD monomer and 28 kD dimer). The mediation models analyses suggested that the effect of WTD on anxiety-like behaviour was driven by hippocampal BDNF, this mediation of effect was region-dependent. Our results also suggested that mature BDNF forms (14 kD and 28 kD) were responsible. The present work brought light to a possible new role for mature BDNF, although it is generally associated with beneficial features, it can also be part of the genesis of anxiety-like behaviours and sociability aspects on WTD models.

Proinflammatory State in the Odontogenesis of Fetuses Exposed to Different Types of Fatty Acids during Pregnancy.

OBJECTIVES: The aim of the present study was to analyze the possible changes caused by the maternal ingestion of different types of fatty acids during pregnancy in the proinflammatory state in the odontogenesis of the fetuses. SUBJECT AND METHODS: Twenty-four jaws (n = 6 per group) of Wistar rats were collected on the 20th day of intrauterine life. Mothers were separated on the first day of pregnancy into 4 groups according to diet, as described below: control group (C) - diet with soy oil as a source of fat; saturated fatty acid group (S) - diet with lard in saturated fatty acids; trans-fatty acid group (T) - diet with vegetable fat, rich in trans-saturated fatty acids; and polyunsaturated fatty acid (PUFA) group - diet with fish oil, rich in PUFAs. RESULTS: Microscopic analysis showed no alterations in tissue development of the teeth between the groups with different lipid diets (T, S, and PUFA) when compared to the control group (C); immunohistochemical analysis for the expression of JAK2, STAT3, P-STAT3, SOCS3, and IL-6 showed no statistically significant difference (p > 0.05) compared to the control group. However, there were changes (p < 0.05) between the T group and the PUFA group in the expression of JAK2. CONCLUSION: Thus, lipid consumption in the maternal diet remains a topic to be explored in embryonic development, despite not causing morphological changes to the tooth germ of rats.

IL10/AMPK pathway was associated with the hippocampal anti-inflammatory response to high-sugar and high-fat diet withdrawal.

OBJECTIVE: The present experimental study aimed to evaluate the effect of consuming an obesogenic diet (OD) on serum and hippocampal inflammation and proteins related to energy metabolism, alongside, we evaluated how the same parameters responded to an OD withdrawal. SUBJECTS: Thirty male 60-days-old Wistar rats were used. METHODS: The control group (n = 10) was fed the control diet across the whole experiment. The remaining animals were fed a high-sugar/high-fat (HSHF) diet for 30 days (n = 20) and half of them were placed on the control diet for 48 h (n = 10) afterwards. RESULTS: OD intake decreased hippocampal AMPK phosphorylation, although, it did not increase serum inflammation and only increased hippocampal pNFκBp65 levels without any increase in the cytokines assessed. Moreover, OD withdrawal led to higher inflammatory markers in the serum and hippocampus and higher hippocampal AMPK phosphorylation. The mediation models applied suggested that the effect of OD withdrawal on hippocampal inflammation was driven by serum inflammation, which activated the hippocampal IL10/AMPK anti-inflammatory pathway as a response. CONCLUSION: Our analyses suggest that OD withdrawal increases serum inflammation with hippocampal consequent inflammatory alterations. Despite the general assumption that improving diet improves health, this may not be immediate.

Parental High-Fat High-Sugar Diet Intake Programming Inflammatory and Oxidative Parameters of Reproductive Health in Male Offspring.

Parental nutrition can impact the health of future generations, programming the offspring for the development of diseases. The developing germ cells of the offspring could be damaged by the maternal or the paternal environment. The germ cells in development and their function could be affected by nutritional adversity and therefore, harm the health of subsequent generations. The paternal or maternal intake of high-fat diets has been shown to affect the reproductive health of male offspring, leading to imbalance in hypothalamic-pituitary-gonadal axis, testicular oxidative stress, low testosterone production, and changes in sperm count, viability, motility, and morphology. There is a need for studies that address the combined effects of diets with a high-fat and high-sugar (H) content by both progenitors on male reproduction. In this context, our study evaluated epigenetic parameters and the inflammatory response that could be associated to oxidative stress in testis and epididymis of adult offspring. 90 days-old male rats were divided according to the combination of the parental diet: CD (control paternal and maternal diet), HP (H paternal diet and control maternal diet), HM (H maternal diet and control paternal diet) and HPM (H paternal and maternal diet).We evaluated serum levels of testosterone and FSH; testicular gene expression of steroidogenic enzymes Star and Hsd17b3 and epigenetic markers Dnmt1, Dnmt3a, Dnmt3b, and Mecp2; testicular and epididymal levels of TNF-α, IL-6, IL-10, and IL-1ß; testicular and epididymal activity of SOD, CAT, and GST; the oxidative markers MDA and CP; the daily sperm production, sperm transit time, and sperm morphology. Testicular epigenetic parameter, inflammatory response, oxidative balance, and daily sperm production of the offspring were affected by the maternal diet; paternal diet influenced serum testosterone levels, and lower daily sperm production was exacerbated by the interaction effect of both parental intake of high-fat high-sugar diet in the testis. There was isolated maternal and paternal effect in the antioxidant enzyme activity in the cauda epididymis, and an interaction effect of both parents in protein oxidative marker. Maternal effect could also be observed in cytokine production of cauda epididymis, and no morphological effects were observed in the sperm. The potential programming effects of isolated or combined intake of a high-fat high-sugar diet by the progenitors could be observed at a molecular level in the reproductive health of male offspring in early adulthood.

Parental high-fat high-sugar diet programming and hypothalamus adipose tissue axis in male Wistar rats.

PURPOSE: Maternal nutrition during early development and paternal nutrition pre-conception can programme offspring health status. Hypothalamus adipose axis is a target of developmental programming, and paternal and maternal high-fat, high-sugar diet (HFS) may be an important factor that predisposes offspring to develop obesity later in life. This study aims to investigate Wistar rats' maternal and paternal HFS differential contribution on the development, adiposity, and hypothalamic inflammation in male offspring from weaning until adulthood. METHODS: Male progenitors were fed a control diet (CD) or HFS for 10 weeks before mating. After mating, dams were fed CD or HFS only during pregnancy and lactation. Forming the following male offspring groups: CD-maternal and paternal CD; MH-maternal HFS and paternal CD; PH-maternal CD and paternal HFS; PMH-maternal and paternal HFS. After weaning, male offspring were fed CD until adulthood. RESULTS: Maternal HFS diet increased weight, visceral adiposity, and serum total cholesterol levels, and decreased hypothalamic weight in weanling male rats. In adult male offspring, maternal HFS increased weight, glucose levels, and hypothalamic NFκBp65. Paternal HFS diet lowered hypothalamic insulin receptor levels in weanling offspring and glucose and insulin levels in adult offspring. The combined effects of maternal and paternal HFS diets increased triacylglycerol, leptin levels, and hypothalamic inflammation in weanling rats, and increased visceral adiposity in adulthood. CONCLUSION: Male offspring intake of CD diet after weaning reversed part of the effects of parental HFS diet during the perinatal period. However, maternal and paternal HFS diet affected adiposity and hypothalamic inflammation, which remained until adulthood.

Effects of maternal diet-induced obesity on metabolic disorders and age-associated miRNA expression in the liver of male mouse offspring.

OBJECTIVE: This study investigated the effect of maternal obesity on aged-male offspring liver phenotype and hepatic expression of a programmed miRNA. METHODS: A mouse model (C57BL/6 J) of maternal diet-induced obesity was used to investigate fasting-serum metabolites, hepatic lipid content, steatosis, and relative mRNA levels (RT-PCR) and protein expression (Western blotting) of key components involved in hepatic and mitochondrial metabolism in 12-month-old offspring. We also measured hepatic lipid peroxidation, mitochondrial content, fibrosis stage, and apoptosis in the offspring. To investigate potential mechanisms leading to the observed phenotype, we also measured the expression of miR-582 (a miRNA previously implicated in liver cirrhosis) in 8-week-old and 12-month-old offspring. RESULTS: Body weight and composition was similar between 8-week-old offspring, however, 12-month-old offspring from obese mothers had increased body weight and fat mass (19.5 ± 0.8 g versus 10.4 ± 0.9 g, p < 0.001), as well as elevated serum levels of LDL and leptin and hepatic lipid content (21.4 ± 2.1 g versus 12.9 ± 1.8 g, p < 0.01). This was accompanied by steatosis, increased Bax/Bcl-2 ratio, and overexpression of p-SAPK/JNK, Tgfß1, Map3k14, and Col1a1 in the liver. Decreased levels of Bcl-2, p-AMPKα, total AMPKα and mitochondrial complexes were also observed. Maternal obesity was associated with increased hepatic miR-582-3p (p < 0.001) and miR-582-5p (p < 0.05). Age was also associated with an increase in both miR-582-3p and miR-582-5p, however, this was more pronounced in the offspring of obese dams, such that differences were greater in 12-month-old animals (-3p: 7.34 ± 1.35 versus 1.39 ± 0.50, p < 0.0001 and -5p: 4.66 ± 1.16 versus 1.63 ± 0.65, p < 0.05). CONCLUSION: Our findings demonstrate that maternal diet-induced obesity has detrimental effects on offspring body composition as well as hepatic phenotype that may be indicative of accelerated-ageing phenotype. These whole-body and cellular phenotypes were associated with age-dependent changes in expression of miRNA-582 that might contribute mechanistically to the development of metabolic disorders in the older progeny.

Inhibition of Toll Like Signaling Pathway Is Associated With Genomic Instability in Rat Liver Exposed to Crack Cocaine.

BACKGROUND/AIM: The aim of the present study was to investigate the biological effects of subacute crack cocaine exposure in rat liver. MATERIAL AND METHODS: A total of 32 rats were distributed into four groups (n=8): Experimental group 1 (G1) and Experimental group 2 (G2): rats received 18 mg/kg of body weight (b.w) of crack cocaine for 5 days, once a day, group G2 remained 72 h without exposure after the experimental period (5 days)(abstinence); Experimental group 3 (G3): rats received 36 mg/kg of body weight (b.w) of crack cocaine for 5 days, once a day; Control Group (CTRL): rats received only the vehicle (DMSO) administered by the intraperitoneal (i.p) route for 5 days, once a day. RESULTS: All groups exposed to crack cocaine had an increase in the number of micronucleated hepatocytes and binucleated cells only in the highest tested dose (36 mg/kg). Karyolysis had an increase in the 18 mg/kg dose, in the abstinence group (G2), and 36 mg/kg group (G3); whereas pyknotic nuclei had an increase in the G2 group. The group exposed to 18 mg/kg of crack cocaine also showed high 8 OHdG expression. The p-NF-κB p65 protein decreased in the groups exposed to crack cocaine at doses of 18 and 36 mg/kg, as well as in the abstinence group. MyD88 was also found decreased in the group exposed to crack cocaine at 18 mg/kg. CONCLUSION: Crack cocaine inhibited toll like signaling pathway whilst being associated with genomic instability in rat liver cells.

Bioaccessibility and Cellular Uptake of Carotenoids Extracted from Bactris gasipaes Fruit: Differences between Conventional and Ionic Liquid-Mediated Extraction.

Currently, on an industrial scale, synthetic colorants are used in many fields, as well as those extracted with conventional organic solvents (COSs), leading to several environmental issues. Therefore, we developed a sustainable extraction and purification method mediated by ionic liquids (IL), which is considered an alternative high-performance replacement for COSs. Carotenoids are natural pigments with low bioaccessibility (BCT) and bioavailability (BV) but with huge importance to health. To investigate if the BCT and cellular uptake of the carotenoids are modified by the extraction method, we conducted a comparison assay between both extraction procedures (IL vs. COS). For this, we used the Amazonian fruit Bactris gasipaes, a rich source of pro-vitamin A carotenoids, to obtain the extract, which was emulsified and subjected to an in vitro digestion model followed by the Caco-2 cell absorption assay. The bioaccessibility of carotenoids using IL was better than those using COS (33.25%, and 26.84%, respectively). The cellular uptake of the carotenoids extracted with IL was 1.4-fold higher than those extracted using COS. Thus, IL may be a feasible alternative as extraction solvent in the food industry, replacing COS, since, in this study, no IL was present in the final extract.

AMPK in the gut-liver-brain axis and its influence on OP rats in an HSHF intake and WTD rat model.

Obesogenic diets (ODs) can affect AMPK activation in several sites as the colon, liver, and hypothalamus. OD intake can impair the hypothalamic AMPK regulation of energy homeostasis. Despite consuming ODs, not all subjects have the propensity to develop or progress to obesity. The obesity propensity is more associated with energy intake than expenditure dysregulations and may have a link with AMPK activity. While the effects of ODs are studied widely, few evaluate the short-term effects of terminating OD intake. Withdrawing from OD (WTD) is thought to improve or reverse the damages caused by the intake. Therefore, here we applied an OD intake and WTD protocol aiming to evaluate AMPK protein content and phosphorylation in the colon, liver, and hypothalamus and their relationship with obesity propensity. To this end, male Wistar rats (60 days) received control or high-sugar/high-fat (HSHF) OD for 30 days. Half of the animals were OD-withdrawn and fed the control diet for 48 h. After intake, we found a reduction in AMPK phosphorylation in the hypothalamus and colon, and after WTD, we found an increase in its hepatic and hypothalamic phosphorylation. The decrease in colon pAMPK/AMPK could be linked with hypothalamic pAMPK/AMPK after HSHF intake, while the increase in hepatic pAMPK/AMPK could have prevented the increase in hypothalamic pAMPK/AMPK. In the obesity-prone rats, we found higher levels of hypothalamic and colon pAMPK/AMPK despite the higher body mass gain. Our results highlight the relevance in multi-organ investigations and animal phenotype evaluation when studying the energy metabolism regulations.