Increased locomotor activity in mice lacking the low-density lipoprotein receptor

Elder, Gregory A.; Ragnauth, Andre; Dorr, Nathan; Franciosi, Sonia; Schmeidler, James; Haroutunian, Vahram; Buxbaum, Joseph D.

doi:10.1016/j.bbr.2008.03.036

Cited by 37 publications

(36 citation statements)

References 35 publications

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“…This augmented T cell response occurred in the absence of any excess weight gain or IL-6 production, indicating that a diet-induced proinflammatory environment did not cause the altered T cell response. This is because LDLr 2/2 mice gain less weight and fat mass when fed a WHF diet compared with LDLr +/+ mice on the same background and are thus less prone to obesity and obesity-induced inflammation (45)(46)(47). Of interest, an acute dietary intervention of 1 wk did not alter the T cell response in CHS, likely because the lipid composition of T cells had not changed after 1 wk of WHF diet and/or owing to enhanced (polarized) innate inflammatory responses to the acute high-fat feeding (48), at the expense of a lower T cell response.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

Pollock

Tedla

Hancock

et al. 2016

The Journal of Immunology

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Although it is recognized that lipids and membrane organization in T cells affect signaling and T cell activation, to what extent dietary lipids alter T cell responsiveness in the absence of obesity and inflammation is not known. In this study, we fed low-density lipoprotein receptor knockout mice a Western high-fat diet for 1 or 9 wk and examined T cell responses in vivo along with T cell lipid composition, membrane order, and activation ex vivo. Our data showed that high levels of circulating lipids for a prolonged period elevated CD4+ and CD8+ T cell proliferation and resulted in an increased proportion of CD4+ central-memory T cells within the draining lymph nodes following induction of contact hypersensitivity. In addition, the 9-wk Western high-fat diet elevated the total phospholipid content and monounsaturated fatty acid level, but decreased saturated phosphatidylcholine and sphingomyelin within the T cells. The altered lipid composition in the circulation, and of T cells, was also reflected by enhanced membrane order at the activation site of ex vivo activated T cells that corresponded to increased IL-2 mRNA levels. In conclusion, dietary lipids can modulate T cell lipid composition and responses in lipoprotein receptor knockout mice even in the absence of excess weight gain and a proinflammatory environment.

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Section: Discussionmentioning

confidence: 99%

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

Pollock

Tedla

Hancock

et al. 2016

The Journal of Immunology

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“…In mice, spontaneous activity can be suppressed by a calorie-dense diet within a few days after starting the diet and therefore cannot be attributed to a markedly increased body mass (Bjursell et al, 2008). Instead, dietary fat may modulate locomotor activity through direct actions of circulating lipids on the brain (Elder et al, 2008). It has not been established, however, whether it is the dietary fat per se in the calorie-dense Western diet, or another aspect of the diet such as the increased caloric intake, that is the critical factor that modulates locomotor activity.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

Novak

Escande

Burghardt

et al. 2010

Hormones and Behavior

110

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Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that highcapacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intraparaventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.

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“…LDLr knock out (LDLr−/−) mice show no major deficits in sensory or motor function, but exhibit increased locomotor activity 42 . LDLR−/− mice also show a decrease in learning and memory regardless of diet 43 .…”

Section: Lipoprotein Receptors In the Cnsmentioning

confidence: 99%

What are lipoproteins doing in the brain?

Wang

Eckel

2014

Trends in Endocrinology & Metabolism

191

153

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Lipoproteins in plasma transport lipids between tissues, however, only high density lipoproteins (HDL) appear to traverse the blood brain barrier; thus, lipoproteins found in the brain must be produced within the central nervous system. Apolipoproteins E (ApoE) and ApoJ are the most abundant apolipoproteins in the brain, are mostly synthesized by astrocytes and are found on HDL. In the hippocampus and other brain regions lipoproteins help regulate neurobehavioral functions by processes that are lipoprotein receptor-mediated. Moreover, lipoproteins and their receptors also have roles in the regulation of body weight and energy balance, i.e. through lipoprotein lipase (LPL) and the LDL receptor-related protein (LRP). Thus, understanding lipoproteins and their metabolism in the brain provides a new opportunity with potential therapeutic relevance.

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Increased locomotor activity in mice lacking the low-density lipoprotein receptor

Cited by 37 publications

References 35 publications

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

What are lipoproteins doing in the brain?

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