Effects of Fatty Acids on Cancer, Obesity, and Atherosclerosis

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

Deadline for manuscript submissions: 5 September 2024 | Viewed by 4701

Special Issue Editor

Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Diabetes Institute, Ohio University, Athens, OH 45701, USA
Interests: the roles of apolipoproteins and neuropeptides in the control of lipid metabolism; insulin response; energy homeostasis; pathogenesis of obesity and diabetes diseases

Special Issue Information

Dear Colleagues,

Fatty acids (FAs) are carboxylic acids that act as principal components of fats such as butter, lard, and oils. Structural differences in FA length lead to differences in absorption, transport, and tissue destination. FAs are potent stimuli of intestinal hormones and other factors that regulate lipid and glucose metabolism, energy homeostasis, insulin response, and chronic inflammation. Intake of specific FAs (i.e., monounsaturated FA; omega-3 polyunsaturated FA) elevates energy expenditure to counteract energy surplus and obesity in animals and humans. The partial replacement of specific FAs has been reported to attenuate pro-inflammatory effects to improve metabolic disorders and cancer. Another important research area is the development of models to identify their mechanisms of actions on cancer, obesity, and atherosclerosis. Both in vivo and in vitro models are necessary for better understanding the roles of specific fatty acids and intestinal hormones in elevation of energy expenditure and insulin action, and downregulation of hypertriglyceridemia and chronic inflammation. It will provide an impetus to develop new preventive and therapeutic strategies to counter obesity-related non-alcoholic fatty liver disease, cardiovascular disease, and cancer.

This Special Issue welcomes submissions of the following article types: original research, reviews, and systemics review in clinical research or basic investigation.

Dr. Chunmin Lo
Guest Editor

Manuscript Submission Information

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Keywords

  • fatty acids
  • fatty acid receptors
  • energy expenditure
  • inflammation
  • insulin action
  • intestinal hormones
  • atherosclerosis
  • cancer
  • non-alcoholic fatty liver disease
  • obesity

Published Papers (3 papers)

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Research

15 pages, 3950 KiB  
Article
Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance
by Fei Wang, Chih-Wei Ko, Jie Qu, Dong Wu, Qi Zhu, Min Liu and Patrick Tso
Nutrients 2023, 15(22), 4840; https://doi.org/10.3390/nu15224840 - 20 Nov 2023
Viewed by 962
Abstract
Apolipoprotein A-IV (apoA-IV), synthesized by enterocytes, is potentially involved in regulating lipid absorption and metabolism, food intake, and glucose metabolism. In this study, we backcrossed apoA-IV knockout (apoA-IV−/−) mice onto the 129/SvJ background for eight generations. Compared to the wild-type (WT) [...] Read more.
Apolipoprotein A-IV (apoA-IV), synthesized by enterocytes, is potentially involved in regulating lipid absorption and metabolism, food intake, and glucose metabolism. In this study, we backcrossed apoA-IV knockout (apoA-IV−/−) mice onto the 129/SvJ background for eight generations. Compared to the wild-type (WT) mice, the 129/SvJ apoA-IV−/− mice gained more weight and exhibited delayed glucose clearance even on the chow diet. During a 16-week high-fat diet (20% by weight of fat) study, apoA-IV−/− mice were more obese than the WT mice, which was associated with their increased food intake as well as reduced energy expenditure and physical activity. In addition, apoA-IV−/− mice developed significant insulin resistance (indicated by HOMA-IR) with severe glucose intolerance even though their insulin levels were drastically higher than the WT mice. In conclusion, we have established a model of apoA-IV−/− mice onto the 129/SvJ background. Unlike in the C57BL/6J strain, apoA-IV−/− 129/SvJ mice become significantly more obese and insulin-resistant than WT mice. Our current investigations of apoA-IV in the 129/SvJ strain and our previous studies in the C57BL/6J strain underline the impact of genetic background on apoA-IV metabolic effects. Full article
(This article belongs to the Special Issue Effects of Fatty Acids on Cancer, Obesity, and Atherosclerosis)
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16 pages, 2742 KiB  
Article
Deficiency of apoA-IV in Female 129X1/SvJ Mice Leads to Diet-Induced Obesity, Insulin Resistance, and Decreased Energy Expenditure
by Jie Qu, Dong Wu, Chih-Wei Ko, Qi Zhu, Min Liu and Patrick Tso
Nutrients 2023, 15(21), 4655; https://doi.org/10.3390/nu15214655 - 02 Nov 2023
Viewed by 1039
Abstract
Obesity is one of the main risk factors for cardiovascular diseases, type II diabetes, hypertension, and certain cancers. Obesity in women at the reproductive stage adversely affects contraception, fertility, maternal well-being, and the health of their offspring. Being a major protein component in [...] Read more.
Obesity is one of the main risk factors for cardiovascular diseases, type II diabetes, hypertension, and certain cancers. Obesity in women at the reproductive stage adversely affects contraception, fertility, maternal well-being, and the health of their offspring. Being a major protein component in chylomicrons and high-density lipoproteins, apolipoprotein A-IV (apoA-IV) is involved in lipid metabolism, food intake, glucose homeostasis, prevention against atherosclerosis, and platelet aggregation. The goal of the present study is to determine the impact of apoA-IV deficiency on metabolic functions in 129X1/SvJ female mouse strain. After chronic high-fat diet feeding, apoA-IV−/− mice gained more weight with a higher fat percentage than wild-type (WT) mice, as determined by measuring their body composition. Increased adiposity and adipose cell size were also observed with a microscope, particularly in periovarian fat pads. Based on plasma lipid and adipokine assays, we found that obesity in apoA-IV−/− mice was not associated with hyperlipidemia but with higher leptin levels. Compared to WT mice, apoA-IV deficiency displayed glucose intolerance and elevated insulin levels, according to the data of the glucose tolerance test, and increased HOMA-IR values at fasting, suggesting possible insulin resistance. Lastly, we found obesity in apoA-IV−/− mice resulting from reduced energy expenditure but not food intake. Together, we established a novel and excellent female mouse model for future mechanistic study of obesity and its associated comorbidities. Full article
(This article belongs to the Special Issue Effects of Fatty Acids on Cancer, Obesity, and Atherosclerosis)
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19 pages, 5698 KiB  
Article
Sexual Dimorphism in Lipid Metabolism and Gut Microbiota in Mice Fed a High-Fat Diet
by Qi Zhu, Nathan Qi, Ling Shen, Chunmin C. Lo, Meifeng Xu, Qing Duan, Nicholas J. Ollberding, Zhe Wu, David Y. Hui, Patrick Tso and Min Liu
Nutrients 2023, 15(9), 2175; https://doi.org/10.3390/nu15092175 - 02 May 2023
Cited by 2 | Viewed by 2117
Abstract
The gut microbiome plays an essential role in regulating lipid metabolism. However, little is known about how gut microbiome modulates sex differences in lipid metabolism. The present study aims to determine whether gut microbiota modulates sexual dimorphism of lipid metabolism in mice fed [...] Read more.
The gut microbiome plays an essential role in regulating lipid metabolism. However, little is known about how gut microbiome modulates sex differences in lipid metabolism. The present study aims to determine whether gut microbiota modulates sexual dimorphism of lipid metabolism in mice fed a high-fat diet (HFD). Conventional and germ-free male and female mice were fed an HFD for four weeks, and lipid absorption, plasma lipid profiles, and apolipoprotein levels were then evaluated. The gut microbiota was analyzed by 16S rRNA gene sequencing. After 4-week HFD consumption, the females exhibited less body weight gain and body fat composition and significantly lower triglyceride levels in very-low-density lipoprotein (VLDL) and cholesterol levels in high-density lipoprotein (HDL) compared to male mice. The fecal microbiota analysis revealed that the male mice were associated with reduced gut microbial diversity. The female mice had considerably different microbiota composition compared to males, e.g., enriched growth of beneficial microbes (e.g., Akkermansia) and depleted growth of Adlercreutzia and Enterococcus. Correlation analyses suggested that the different compositions of the gut microbiota were associated with sexual dimorphism in body weight, fat mass, and lipid metabolism in mice fed an HFD. Our findings demonstrated significant sex differences in lipid metabolism and the microbiota composition at baseline (during LFD), along with sex-dependent responses to HFD. A comprehensive understanding of sexual dimorphism in lipid metabolism modulated by microbiota will help to develop more sex-specific effective treatment options for dyslipidemia and metabolic disorders in females. Full article
(This article belongs to the Special Issue Effects of Fatty Acids on Cancer, Obesity, and Atherosclerosis)
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