Abstract
To further understand the role of lipogenesis and lipotoxicity in the development of obesity and diabetes, lipidomes of various organs from ob/ob mice and their wild type controls were analyzed by shotgun lipidomics at 10, 12, and 16 weeks of age. We observed that the amounts of fatty acyl (FA) chains corresponding to those from de novo synthesis (e.g., 16:0, 16:1, and 18:1 FA) were substantially elevated in ob/ob mice, consistent with increased expression of genes and proteins involved in biosynthesis. Polyunsaturated fatty acid species were moderately increased in the examined tissues of ob/ob mice, since they can only be absorbed from diets or elongated from the ingested n-3 or n-6 FA. Different profiles of FA chains between ob/ob mouse liver and skeletal muscle reflect diverging lipogenesis pathways in these organs. Amounts of vaccenic acids (i.e., 18:1(n-7) FA) in 12- and 16-week ob/ob mouse liver were significantly increased compared to their controls, indicating enhanced de novo synthesis of this acid through 16:1(n-7) FA in the liver starting at 12 weeks of age. Coincidentally, synthesis of triacylglycerol from monoacylglycerol in the liver was also increased in ob/ob mice starting at 12 weeks of age, as revealed by simulation of triacylglycerol synthesis. Moreover, levels of lipotoxic lipid classes were significantly higher in ob/ob mice than their age-matched controls, supporting the notion that elevated lipotoxic components are tightly associated with insulin resistance in ob/ob mice. Taken together, the current study revealed that lipogenesis and lipotoxicity in ob/ob mice likely contribute to insulin resistance and provides great insights into the underlying mechanisms of diabetes and obesity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 161-169 |
| Number of pages | 9 |
| Journal | Prostaglandins Leukotrienes and Essential Fatty Acids |
| Volume | 136 |
| DOIs | |
| State | Published - Sep 1 2018 |
| Externally published | Yes |
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Keywords
- Lipidomics
- Lipogenesis
- Lipotoxicity
- ob/ob Mice
- Obesity
- Shotgun lipidomics
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology
Cite this
Lipidomic analysis reveals significant lipogenesis and accumulation of lipotoxic components in ob/ob mouse organs. / Hayakawa, Jun; Wang, Miao; Wang, Chunyan; Han, Rowland H.; Jiang, Zhen Y.; Han, Xianlin.
In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 136, 01.09.2018, p. 161-169.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lipidomic analysis reveals significant lipogenesis and accumulation of lipotoxic components in ob/ob mouse organs
AU - Hayakawa, Jun
AU - Wang, Miao
AU - Wang, Chunyan
AU - Han, Rowland H.
AU - Jiang, Zhen Y.
AU - Han, Xianlin
PY - 2018/9/1
Y1 - 2018/9/1
N2 - To further understand the role of lipogenesis and lipotoxicity in the development of obesity and diabetes, lipidomes of various organs from ob/ob mice and their wild type controls were analyzed by shotgun lipidomics at 10, 12, and 16 weeks of age. We observed that the amounts of fatty acyl (FA) chains corresponding to those from de novo synthesis (e.g., 16:0, 16:1, and 18:1 FA) were substantially elevated in ob/ob mice, consistent with increased expression of genes and proteins involved in biosynthesis. Polyunsaturated fatty acid species were moderately increased in the examined tissues of ob/ob mice, since they can only be absorbed from diets or elongated from the ingested n-3 or n-6 FA. Different profiles of FA chains between ob/ob mouse liver and skeletal muscle reflect diverging lipogenesis pathways in these organs. Amounts of vaccenic acids (i.e., 18:1(n-7) FA) in 12- and 16-week ob/ob mouse liver were significantly increased compared to their controls, indicating enhanced de novo synthesis of this acid through 16:1(n-7) FA in the liver starting at 12 weeks of age. Coincidentally, synthesis of triacylglycerol from monoacylglycerol in the liver was also increased in ob/ob mice starting at 12 weeks of age, as revealed by simulation of triacylglycerol synthesis. Moreover, levels of lipotoxic lipid classes were significantly higher in ob/ob mice than their age-matched controls, supporting the notion that elevated lipotoxic components are tightly associated with insulin resistance in ob/ob mice. Taken together, the current study revealed that lipogenesis and lipotoxicity in ob/ob mice likely contribute to insulin resistance and provides great insights into the underlying mechanisms of diabetes and obesity.
AB - To further understand the role of lipogenesis and lipotoxicity in the development of obesity and diabetes, lipidomes of various organs from ob/ob mice and their wild type controls were analyzed by shotgun lipidomics at 10, 12, and 16 weeks of age. We observed that the amounts of fatty acyl (FA) chains corresponding to those from de novo synthesis (e.g., 16:0, 16:1, and 18:1 FA) were substantially elevated in ob/ob mice, consistent with increased expression of genes and proteins involved in biosynthesis. Polyunsaturated fatty acid species were moderately increased in the examined tissues of ob/ob mice, since they can only be absorbed from diets or elongated from the ingested n-3 or n-6 FA. Different profiles of FA chains between ob/ob mouse liver and skeletal muscle reflect diverging lipogenesis pathways in these organs. Amounts of vaccenic acids (i.e., 18:1(n-7) FA) in 12- and 16-week ob/ob mouse liver were significantly increased compared to their controls, indicating enhanced de novo synthesis of this acid through 16:1(n-7) FA in the liver starting at 12 weeks of age. Coincidentally, synthesis of triacylglycerol from monoacylglycerol in the liver was also increased in ob/ob mice starting at 12 weeks of age, as revealed by simulation of triacylglycerol synthesis. Moreover, levels of lipotoxic lipid classes were significantly higher in ob/ob mice than their age-matched controls, supporting the notion that elevated lipotoxic components are tightly associated with insulin resistance in ob/ob mice. Taken together, the current study revealed that lipogenesis and lipotoxicity in ob/ob mice likely contribute to insulin resistance and provides great insights into the underlying mechanisms of diabetes and obesity.
KW - Lipidomics
KW - Lipogenesis
KW - Lipotoxicity
KW - ob/ob Mice
KW - Obesity
KW - Shotgun lipidomics
UR - http://www.scopus.com/inward/record.url?scp=85009470018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85009470018&partnerID=8YFLogxK
U2 - 10.1016/j.plefa.2017.01.002
DO - 10.1016/j.plefa.2017.01.002
M3 - Article
C2 - 28110829
AN - SCOPUS:85009470018
VL - 136
SP - 161
EP - 169
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
SN - 0952-3278
ER -