Dataset Information

Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice.

ABSTRACT:

Background

Obesity is associated with reduced levels of circulating high-density lipoproteins (HDLs) and its major protein, apolipoprotein (apo) A-I. As a result of the role of HDL and apoA-I in cellular lipid transport, low HDL and apoA-I may contribute directly to establishing or maintaining the obese condition.

Methods

To test this, male C57BL/6 wild-type (WT), apoA-I deficient (apoA-I(-/-)) and apoA-I transgenic (apoA-I(tg/tg)) mice were fed obesogenic diets (ODs) and monitored for several clinical parameters. We also performed cell culture studies.

Results

ApoA-I(-/-) mice gained significantly more body weight and body fat than WT mice over 20 weeks despite their reduced food intake. During a caloric restriction regime imposed on OD-fed mice, apoA-I deficiency significantly inhibited the loss of body fat as compared with WT mice. Reduced body fat loss with caloric restriction in apoA-I(-/-) mice was associated with blunted stimulated adipose tissue lipolysis as verified by decreased levels of phosphorylated hormone-sensitive lipase (p-HSL) and lipolytic enzyme mRNA. In contrast to apoA-I(-/-) mice, apoA-I(tg/tg) mice gained relatively less weight than WT mice, consistent with other reports. ApoA-I(tg/tg) mice showed increased adipose tissue lipolysis, verified by increased levels of p-HSL and lipolytic enzyme mRNA. In cell culture studies, HDL and apoA-I specifically increased catecholamine-induced lipolysis possibly through modulating the adipocyte plasma membrane cholesterol content.

Conclusions

Thus, apoA-I and HDL contribute to modulating body fat content by controlling the extent of lipolysis. ApoA-I and HDL are key components of lipid metabolism in adipose tissue and constitute new therapeutic targets in obesity.

SUBMITTER: Wei H

PROVIDER: S-EPMC3940828 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice.

Wei H H Averill M M MM McMillen T S TS Dastvan F F Mitra P P Subramanian S S Tang C C Chait A A Leboeuf R C RC

Nutrition & diabetes 20140224

<h4>Background</h4>Obesity is associated with reduced levels of circulating high-density lipoproteins (HDLs) and its major protein, apolipoprotein (apo) A-I. As a result of the role of HDL and apoA-I in cellular lipid transport, low HDL and apoA-I may contribute directly to establishing or maintaining the obese condition.<h4>Methods</h4>To test this, male C57BL/6 wild-type (WT), apoA-I deficient (apoA-I(-/-)) and apoA-I transgenic (apoA-I(tg/tg)) mice were fed obesogenic diets (ODs) and monitore ...[more]

PMID: 24567123

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Project description:Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.

Project description:BackgroundICU-acquired weakness is a debilitating consequence of prolonged critical illness that is associated with poor outcome. Recently, premorbid obesity has been shown to protect against such illness-induced muscle wasting and weakness. Here, we hypothesized that this protection was due to increased lipid and ketone availability.MethodsIn a centrally catheterized, fluid-resuscitated, antibiotic-treated mouse model of prolonged sepsis, we compared markers of lipolysis and fatty acid oxidation in lean and obese septic mice (n = 117). Next, we compared markers of muscle wasting and weakness in septic obese wild-type and adipose tissue-specific ATGL knockout (AAKO) mice (n = 73), in lean septic mice receiving either intravenous infusion of lipids or standard parenteral nutrition (PN) (n = 70), and in lean septic mice receiving standard PN supplemented with either the ketone body 3-hydroxybutyrate or isocaloric glucose (n = 49).ResultsObese septic mice had more pronounced lipolysis (p ≤ 0.05), peripheral fatty acid oxidation (p ≤ 0.05), and ketogenesis (p ≤ 0.05) than lean mice. Blocking lipolysis in obese septic mice caused severely reduced muscle mass (32% loss vs. 15% in wild-type, p < 0.001) and specific maximal muscle force (59% loss vs. 0% in wild-type; p < 0.001). In contrast, intravenous infusion of lipids in lean septic mice maintained specific maximal muscle force up to healthy control levels (p = 0.6), whereas this was reduced with 28% in septic mice receiving standard PN (p = 0.006). Muscle mass was evenly reduced with 29% in both lean septic groups (p < 0.001). Lipid administration enhanced fatty acid oxidation (p ≤ 0.05) and ketogenesis (p < 0.001), but caused unfavorable liver steatosis (p = 0.01) and a deranged lipid profile (p ≤ 0.01). Supplementation of standard PN with 3-hydroxybutyrate also attenuated specific maximal muscle force up to healthy control levels (p = 0.1), but loss of muscle mass could not be prevented (25% loss in both septic groups; p < 0.001). Importantly, this intervention improved muscle regeneration markers (p ≤ 0.05) without the unfavorable side effects seen with lipid infusion.ConclusionsObesity-induced muscle protection during sepsis is partly mediated by elevated mobilization and metabolism of endogenous fatty acids. Furthermore, increased availability of ketone bodies, either through ketogenesis or through parenteral infusion, appears to protect against sepsis-induced muscle weakness also in the lean.

Dataset Information

Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice.

Background

Methods

Results

Conclusions

Publications

Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice.

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