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Nutritional Regulation of Insulin Resistance and Lipid Metabolism

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Lipids".

Deadline for manuscript submissions: closed (20 April 2023) | Viewed by 29771

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Dr. Montserrat Esteve

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Guest Editor

Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Barcelona, Spain
Interests: energy metabolism; adipose tissue; obesity; metabolic syndrome; diet induced obesity; food intake; glucorticosteroids; inflammation
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Dr. Maria del Mar Romero

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Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Barcelona, Spain
Interests: nutrition; insulin resistance; metabolic diseases; lipid metabolism; glucose metabolism; obesity; metabolic syndrome; energy metabolism; adipose tissue; adipocytes; intermittent fasting; 11-beta-hydroxysteroid dehydrogenases; food restriction
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Special Issue Information

Dear Colleagues,

Insulin resistance is one of the risk factors associated with obesity that is relevant to the development of metabolic syndrome (MetS). In fact, MetS is the group of determining risk factors leading to heart disease and stroke, being the leading cause of death in the world. It is known that lipid metabolism plays an important role in the development of insulin resistance. Thus, the type of diet, and therefore the components of the food (nutrients and non-nutrients), has a determining role in the regulation of metabolism, as well as in the development of insulin resistance. Numerous studies show that food components have biological effects at different levels, ranging from microbiota changes and regulating insulin resistance through the intestinal-brain axis to gene expression regulation.

In this Topic, we invite researchers to submit novelty papers on the effects of nutritional compounds related to lipid metabolism and insulin resistance. We welcome original research articles, animal and clinical studies, as well as review articles.

Dr. Montserrat Esteve
Dr. Maria del Mar Romero
Guest Editors

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Keywords

insulin resistance
lipid metabolism
signal pathways
fatty acids
carbohydrates and sugars
bioactive food compounds
diabetes
obesity
metabolic syndrome

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Published Papers (10 papers)

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Research

25 pages, 11863 KiB

Open AccessArticle

A Novel Tetrapeptide Ala-Phe-Phe-Pro (AFFP) Derived from Antarctic Krill Prevents Scopolamine-Induced Memory Disorder by Balancing Lipid Metabolism of Mice Hippocampus

by Jingqi Yang, Yan Qi, Beiwei Zhu and Songyi Lin

Nutrients 2024, 16(7), 1019; https://doi.org/10.3390/nu16071019 - 31 Mar 2024

Viewed by 1354

Abstract

Memory impairment is a serious problem with organismal aging and increased social pressure. The tetrapeptide Ala-Phe-Phe-Pro (AFFP) is a synthetic analogue of Antarctic krill derived from the memory-improving Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) after digestion and absorption. The objective of this research was to assess the neuroprotective effects of AFFP by reducing oxidative stress and controlling lipid metabolism in the brains of mice with memory impairment caused by scopolamine. The 1H Nuclear magnetic resonance spectroscopy results showed that AFFP had three active hydrogen sites that could contribute to its antioxidant properties. The findings from in vivo tests demonstrated that AFFP greatly enhanced the mice’s behavioral performance in the passive avoidance, novel object recognition, and eight-arm maze experiments. AFFP reduced oxidative stress by enhancing superoxide dismutase activity and malondialdehyde levels in mice serum, thereby decreasing reactive oxygen species level in the mice hippocampus. In addition, AFFP increased the unsaturated lipid content to balance the unsaturated lipid level against the neurotoxicity of the mice hippocampus. Our findings suggest that AFFP emerges as a potential dietary intervention for the prevention of memory impairment disorders. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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18 pages, 6715 KiB

Open AccessArticle

Sex-Dependent Metabolic Effects in Diet-Induced Obese Rats following Intermittent Fasting Compared with Continuous Food Restriction

by Laia Bosch de Basea, Marina Boguñà, Alicia Sánchez, Montserrat Esteve, Mar Grasa and Maria del Mar Romero

Nutrients 2024, 16(7), 1009; https://doi.org/10.3390/nu16071009 - 29 Mar 2024

Viewed by 1422

Abstract

Recently, intermittent fasting has gained relevance as a strategy to lose weight and improve health as an alternative to continuous caloric restriction. However, the metabolic impact and the sex-related differences are not fully understood. The study aimed to compare the response to a continuous or intermittent caloric restriction in male and female rats following a previous induction of obesity through a cafeteria diet by assessing changes in body weight, energy intake, metabolic parameters, and gene expression in liver hepatic and adipose tissue. The continuous restriction reduced the energy available by 30% and the intermittent restriction consisted of a 75% energy reduction on two non-consecutive days per week. The interventions reduced body weight and body fat in both sexes, but the loss of WAT in females was more marked in both models of caloric restriction, continuous and intermittent. Both caloric restrictions improved insulin sensitivity, but more markedly in females, which showed a more pronounced decrease in HOMA-IR score and an upregulation of hepatic IRS2 and Sirt1 gene expression that was not observed in males. These findings suggest the fact that females are more sensitive than males to reduced caloric content in the diet. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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23 pages, 2948 KiB

Open AccessArticle

Dietary Docosahexaenoic Acid and Glucose Systemic Metabolic Changes in the Mouse

by Bruce A. Watkins, John W. Newman, George A. Kuchel, Oliver Fiehn and Jeffrey Kim

Nutrients 2023, 15(12), 2679; https://doi.org/10.3390/nu15122679 - 8 Jun 2023

Cited by 2 | Viewed by 2105

Abstract

The endocannabinoid system (ECS) participates in regulating whole body energy balance. Overactivation of the ECS has been associated with the negative consequence of obesity and type 2 diabetes. Since activators of the ECS rely on lipid-derived ligands, an investigation was conducted to determine whether dietary PUFA could influence the ECS to affect glucose clearance by measuring metabolites of macronutrient metabolism. C57/blk6 mice were fed a control or DHA-enriched semi-purified diet for a period of 112 d. Plasma, skeletal muscle, and liver were collected after 56 d and 112 d of feeding the diets for metabolomics analysis. Key findings characterized a shift in glucose metabolism and greater catabolism of fatty acids in mice fed the DHA diet. Glucose use and promotion of fatty acids as substrate were found based on levels of metabolic pathway intermediates and altered metabolic changes related to pathway flux with DHA feeding. Greater levels of DHA-derived glycerol lipids were found subsequently leading to the decrease of arachidonate-derived endocannabinoids (eCB). Levels of 1- and 2-arachidonylglcerol eCB in muscle and liver were lower in the DHA diet group compared to controls. These findings demonstrate that DHA feeding in mice alters macronutrient metabolism and may restore ECS tone by lowering arachidonic acid derived eCB. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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14 pages, 2770 KiB

Open AccessArticle

β-Hydroxy-β-methyl Butyrate Regulates the Lipid Metabolism, Mitochondrial Function, and Fat Browning of Adipocytes

by Geyan Duan, Changbing Zheng, Jiayi Yu, Peiwen Zhang, Mengliao Wan, Jie Zheng and Yehui Duan

Nutrients 2023, 15(11), 2550; https://doi.org/10.3390/nu15112550 - 30 May 2023

Cited by 2 | Viewed by 2439

Abstract

A growing number of in vivo studies demonstrated that β-hydroxy-β-methyl butyrate (HMB) can serve as a lipid-lowering nutrient. Despite this interesting observation, the use of adipocytes as a model for research is yet to be explored. To ascertain the effects of HMB on the lipid metabolism of adipocytes and elucidate the underlying mechanisms, the 3T3-L1 cell line was employed. Firstly, serial doses of HMB were added to 3T3-L1 preadipocytes to evaluate the effects of HMB on cell proliferation. HMB (50 µM) significantly promoted the proliferation of preadipocytes. Next, we investigated whether HMB could attenuate fat accumulation in adipocytes. The results show that HMB treatment (50 µM) reduced the triglyceride (TG) content. Furthermore, HMB was found to inhibit lipid accumulation by suppressing the expression of lipogenic proteins (C/EBPα and PPARγ) and increasing the expression of lipolysis-related proteins (p-AMPK, p-Sirt1, HSL, and UCP3). We also determined the concentrations of several lipid metabolism-related enzymes and fatty acid composition in adipocytes. The HMB-treated cells showed reduced G6PD, LPL, and ATGL concentrations. Moreover, HMB improved the fatty acid composition in adipocytes, manifested by increases in the contents of n6 and n3 PUFAs. The enhancement of the mitochondrial respiratory function of 3T3-L1 adipocytes was confirmed via Seahorse metabolic assay, which showed that HMB treatment elevated basal mitochondrial respiration, ATP production, H⁺ leak, maximal respiration, and non-mitochondrial respiration. In addition, HMB enhanced fat browning of adipocytes, and this effect might be associated with the activation of the PRDM16/PGC-1α/UCP1 pathway. Taken together, HMB-induced changes in the lipid metabolism and mitochondrial function may contribute to preventing fat deposition and improving insulin sensitivity. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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23 pages, 5430 KiB

Open AccessArticle

Regulation of Insulin Resistance, Lipid Profile and Glucose Metabolism Associated with Polycystic Ovary Syndrome by Tinospora cordifolia

by Ritu Rani, Havagiray R. Chitme, Neha Kukreti, Pankaj Pant, Basel A. Abdel-Wahab, Masood Medleri Khateeb, Mohammed Shafiuddin Habeeb and Marwa B. Bakir

Nutrients 2023, 15(10), 2238; https://doi.org/10.3390/nu15102238 - 9 May 2023

Cited by 5 | Viewed by 3604

Abstract

Background: The plant Tinospora cordifolia (TC), traditionally known as guduchi or giloy, is used for a number of health conditions as a nutritional supplement and rejuvenation medicine. Its nutritional supplementary products are traditionally recommended for a wide range of health issues, including diabetes, menstruation discomfort, fever, obesity, inflammation, and more. Unfortunately, there has not been extensive research into its effectiveness in treating or managing insulin resistance, lipid and carbohydrate metabolism, hormonal imbalance, and metabolic syndrome-associated polycystic ovary syndrome (PCOS). Methods: Consequently, the present study was designed to induce insulin resistance, dyslipidemia, hormonal abnormality, hyperglycemia, and menstrual disturbance of PCOS using dehydroepiandrosterone (DHEA) in mice and study the effect of oral TC extracts on these factors by using ancient and modern technologies. During the 21-day study, 6 mg/100 g/day of DHEA was given to female mice. Levels of glucose, insulin, lipids, and hormones were estimated. In addition to being seen with the naked eye, the morphological and microscopic changes were also observed on histology slides. Results: The study outcomes show that pretreatment with TC preparations significantly improved biochemical and histological abnormalities in female mice. Diestrus phase was only observed in DHEA-treated animals, while cornified epithelial cells were present in TC-treated mice. Pretreatment with TC satva showed significant (p < 0.001) reductions in body weight compared to placebo. Fasting blood glucose, 1-h OGTT, and 2-h OGTT levels were all significantly lower in TC satva- and oil-treated animals in comparison to the disease control group (p < 0.001). Treatment with TC extracts resulted in a normalization of estradiol, progesterone, and testosterone levels (p < 0.05). Treatment with TC extract improved lipid profiles (p < 0.001), LH/FSH ratios (p < 0.01), fasting insulin levels (p < 0.001), HOMA-IR (p < 0.001), HOMA-Beta (p < 0.001), and QUICKI (p < 0.001). Both macroscopic and microscopic alterations were seen to be restored after TC extract treatment. After being treated with TC satva, oil, and hydroalcoholic extract, the severity of PCOS decreased by 54.86%. Conclusions: These findings lead us to the conclusion that TC extracts and satva as nutritional supplements are useful for treating PCOS and associated symptoms. It is recommended that additional research be conducted to determine the molecular mechanism of action of TC nutritional supplements on PCOS-related changes in metabolic profiles. We also recommend further clinical studies to explore the clinical efficacy and effectiveness of TC nutritional supplements in treating and/or managing PCOS. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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13 pages, 285 KiB

Open AccessArticle

Relationship between Coffee, Tea, and Carbonated Beverages and Cardiovascular Risk Factors

by Hye-Ji An, Yejin Kim and Young-Gyun Seo

Nutrients 2023, 15(4), 934; https://doi.org/10.3390/nu15040934 - 13 Feb 2023

Cited by 4 | Viewed by 3072

Abstract

We aimed to analyze the relationship between coffee, tea, and carbonated beverages and cardiovascular risk factors. We used data from the fourth to eighth Korea National Health and Nutrition Examination Surveys (2007–2016, 2019–2020). We categorized the frequency of intake into three groups (<1 time/week, 1 time/week to <1 time/day, and ≥1 time/day). Subsequently, logistic regression analyses by sex were performed to assess cardiovascular risk factors (hypertension (HTN), diabetes mellitus (DM), dyslipidemia (DL), or metabolic syndrome (MetS)) according to the frequency of coffee, tea, and carbonated beverage intake. For HTN, coffee intake showed an inverse relationship and tea intake showed a direct relationship. For DM, coffee intake showed an inverse relationship, and tea and carbonated beverage intake showed a direct relationship. For DL, coffee intake showed an inverse relationship, whereas tea intake demonstrated a direct relationship. In addition, carbonated beverage intake showed a direct relationship with MetS. Coffee intake showed an inverse relationship with HTN, DM, and DL. However, tea intake showed a direct relationship with HTN, DM, and DL, whereas carbonated beverage intake showed a direct relationship with DM and MetS. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

18 pages, 5485 KiB

Open AccessArticle

Protective Effect of Vegan Microbiota on Liver Steatosis Is Conveyed by Dietary Fiber: Implications for Fecal Microbiota Transfer Therapy

by Nikola Daskova, Marie Heczkova, Istvan Modos, Jaromir Hradecky, Tomas Hudcovic, Marek Kuzma, Helena Pelantova, Irena Buskova, Eva Sticova, David Funda, Jaroslav Golias, Barbora Drabonova, Jarmila Jarkovska, Maria Kralova, Ivana Cibulkova, Jan Gojda and Monika Cahova

Nutrients 2023, 15(2), 454; https://doi.org/10.3390/nu15020454 - 15 Jan 2023

Cited by 2 | Viewed by 3681

Abstract

Fecal microbiota transfer may serve as a therapeutic tool for treating obesity and related disorders but currently, there is no consensus regarding the optimal donor characteristics. We studied how microbiota from vegan donors, who exhibit a low incidence of non-communicable diseases, impact on metabolic effects of an obesogenic diet and the potential role of dietary inulin in mediating these effects. Ex-germ-free animals were colonized with human vegan microbiota and fed a standard or Western-type diet (WD) with or without inulin supplementation. Despite the colonization with vegan microbiota, WD induced excessive weight gain, impaired glucose metabolism, insulin resistance, and liver steatosis. However, supplementation with inulin reversed steatosis and improved glucose homeostasis. In contrast, inulin did not affect WD-induced metabolic changes in non-humanized conventional mice. In vegan microbiota-colonized mice, inulin supplementation resulted in a significant change in gut microbiota composition and its metabolic performance, inducing the shift from proteolytic towards saccharolytic fermentation (decrease of sulfur-containing compounds, increase of SCFA). We found that (i) vegan microbiota alone does not protect against adverse effects of WD; and (ii) supplementation with inulin reversed steatosis and normalized glucose metabolism. This phenomenon is associated with the shift in microbiota composition and accentuation of saccharolytic fermentation at the expense of proteolytic fermentation. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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12 pages, 1502 KiB

Open AccessArticle

A Comparison of Primary Human Hepatocytes and Hepatoma Cell Lines to Model the Effects of Fatty Acids, Fructose and Glucose on Liver Cell Lipid Accumulation

by Zoë J. Huggett, Alison Smith, Nicola De Vivo, Dhanny Gomez, Preeti Jethwa, John M. Brameld, Andrew Bennett and Andrew M. Salter

Nutrients 2023, 15(1), 40; https://doi.org/10.3390/nu15010040 - 21 Dec 2022

Cited by 9 | Viewed by 4370

Abstract

Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We investigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different cell lines: HepG2 (human hepatoblastoma–derived cell line), Huh7 (human hepatocellular carcinoma cell line) and McA-RH7777 (McA, rat hepatocellular carcinoma cell line). Cells were treated for 48 h with fatty acids (0 or 200 μM), glucose (5 mM or 11 mM) and fructose (0 mM, 2 mM or 8 mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (p < 0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11 mM glucose plus fatty acids (p = 0.004, fatty acid × glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (p < 0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (p = 0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (p < 0.001 for fatty acid × insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (p < 0.001 insulin × cell type interaction). Hence, glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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15 pages, 963 KiB

Open AccessArticle

TG/HDL Ratio Is an Independent Predictor for Estimating Resting Energy Expenditure in Adults with Normal Weight, Overweight, and Obesity

by Annaliese Widmer, Margaret G. Mercante and Heidi J. Silver

Nutrients 2022, 14(23), 5106; https://doi.org/10.3390/nu14235106 - 1 Dec 2022

Cited by 2 | Viewed by 3799

Abstract

Factors that determine resting energy expenditure (REE) remain under investigation, particularly in persons with a high body mass index (BMI). The accurate estimation of energy expenditure is essential for conducting comprehensive nutrition assessments, planning menus and meals, prescribing weight and chronic disease interventions, and the prevention of malnutrition. This study aimed to: (a) determine the contribution of cardiometabolic biomarkers to the inter-individual variation in REE in persons categorized by BMI; and (b) assess the contribution of these biomarkers in the prediction of REE when persons of varying BMI status were categorized by their glycemic and metabolic syndrome status. Baseline data from 645 adults enrolled in diet intervention trials included REE measured by indirect calorimetry, body composition by dual energy X-ray absorptiometry, anthropometrics, and cardiometabolic biomarkers. Multivariate linear regression modeling was conducted to determine the most parsimonious model that significantly predicted REE by BMI category, metabolic syndrome status, and glycemic status. Modeling with the traditional predictors (age, sex, height, weight) accounted for 58–63% of the inter-individual variance in REE. When including age, sex, height, weight and fat-free mass as covariates, adding TG/HDL to regression modeling accounted for 71–87% of the variance in REE. The finding that TG/HDL is an independent predictor in estimating REE was further confirmed when participants were categorized by metabolic syndrome status and by glycemic status. The clinical utility of calculating the TG/HDL ratio not only aids health care providers in identifying patients with impaired lipid metabolism but can optimize the estimation of REE to better meet therapeutic goals for weight and disease management. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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15 pages, 6180 KiB

Open AccessArticle

Reduction in Insulin Mediated ERK Phosphorylation by Palmitate in Liver Cells Is Independent of Fatty Acid Induced ER Stress

by Sindiyan Alshaikh Mubarak, Abeer Al Otaibi, Ali Al Qarni, Ahmed Bakillah and Jahangir Iqbal

Nutrients 2022, 14(17), 3641; https://doi.org/10.3390/nu14173641 - 2 Sep 2022

Cited by 3 | Viewed by 2514

Abstract

Saturated free fatty acids (FFAs) such as palmitate in the circulation are known to cause endoplasmic reticulum (ER) stress and insulin resistance in peripheral tissues. In addition to protein kinase B (AKT) signaling, extracellular signal-regulated kinase (ERK) has been implicated in the development of insulin resistance. However, there are conflicting data regarding role of ERK signaling in ER stress-induced insulin resistance. In this study, we investigated the effects of ER stress on insulin resistance and ERK phosphorylation in Huh-7 cells and evaluated how oleate prevents palmitate-mediated ER stress. Treatment with insulin resulted in an increase of 38–45% in the uptake of glucose in control cells compared to non-insulin-treated control cells, along with an increase in the phosphorylation of AKT and ERK. We found that treatment with palmitate increased the expression of ER stress genes, including the splicing of X box binding protein 1 (XBP1) mRNA. At the same time, we observed a decrease in insulin-mediated uptake of glucose and ERK phosphorylation in Huh-7 cells, without any change in AKT phosphorylation. Supplementation of oleate along with palmitate mitigated the palmitate-induced ER stress but did not affect insulin-mediated glucose uptake or ERK phosphorylation. The findings of this study suggest that palmitate reduces insulin-mediated ERK phosphorylation in liver cells and this effect is independent of fatty-acid-induced ER stress. Full article

(This article belongs to the Special Issue Nutritional Regulation of Insulin Resistance and Lipid Metabolism)

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