scholarly journals Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis

2021 ◽  
Vol 22 (23) ◽  
pp. 12967
Author(s):  
Jennifer L. Myers ◽  
Maria Porter ◽  
Nicholas Narwold ◽  
Krishna Bhat ◽  
Brigitte Dauwalder ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Dietary Cholesterol ◽  
Olfactory Learning ◽  
Cholesterol Homeostasis ◽  
Cholesterol Diet ◽  
Olfactory Conditioning ◽  
Olfactory Memory ◽  
Conditioning Paradigm ◽  
Visual Defects ◽  
Low Cholesterol

Drosophila’s white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

scholarly journals Nuclear Receptor DHR96 Acts as a Sentinel for Low Cholesterol Concentrations in Drosophila melanogaster

2009 ◽  
Vol 30 (3) ◽  
pp. 793-805 ◽  
Author(s):  
Mattéa Bujold ◽  
Akila Gopalakrishnan ◽  
Emma Nally ◽  
Kirst King-Jones
Keyword(s):  
Dietary Cholesterol ◽  
Transcriptional Response ◽  
Cholesterol Homeostasis ◽  
Critical Threshold ◽  
High Cholesterol Diet ◽  
Cholesterol Levels ◽  
Wide Range ◽  
Type C ◽  
Niemann Pick ◽  
Low Cholesterol

ABSTRACT All eukaryotic cells have to maintain cholesterol concentrations within defined margins in order to function normally. Perturbing cholesterol homeostasis can result in a wide range of cellular and systemic defects, including cardiovascular diseases, as well as Niemann-Pick and Tangier diseases. Here, we show that DHR96 is indispensable for mediating the transcriptional response to dietary cholesterol and that it acts as a key regulator of the Niemann-Pick type C gene family, as well as of other genes involved in cholesterol uptake, metabolism, and transport. DHR96 mutants are viable and phenotypically normal on a standard medium but fail to survive on diets that are low in cholesterol. DHR96 mutants have aberrant cholesterol levels, demonstrating a defect in maintaining cholesterol homeostasis. Remarkably, we found that a high-cholesterol diet phenocopied the genomic profile of the DHR96 mutation, indicating that DHR96 resides at the top of a genetic hierarchy controlling cholesterol homeostasis in insects. We propose a model whereby DHR96 is activated when cellular cholesterol concentrations drop below a critical threshold in order to protect cells from severe cholesterol deprivation.

Relation of dietary cholesterol and fat to atheromatosis in laying and nonlaying hens

1961 ◽  
Vol 200 (1) ◽  
pp. 71-74 ◽  
Author(s):  
A. C. Ivy ◽  
C. S. N. Setty ◽  
R. Suzuki
Keyword(s):  
High Fat Diet ◽  
Dietary Cholesterol ◽  
Relative Energy ◽  
Egg Laying ◽  
The Other ◽  
Cholesterol Diet ◽  
High Fat ◽  
One Year ◽  
Low Cholesterol ◽  
Rate Of Accumulation

Twenty-four female chicks received a diet containing 0.05% cholesterol, 3% fat and 22% protein for 6 months. Then, 12 of them, 6 good layers and 6 non- or poor layers, received a diet containing 0.03% cholesterol, 2.4% fat and 14.25% protein for 52 weeks. The other 12 received a diet containing 0.08% cholesterol, 7% fat (6.5 gm/100 gm of diet being beef tallow, m.p. 42°C) and 17.44% protein, the relative energy values being 774 and 1001 calories, respectively. These diets were fed 12 months, at the end of which period the chickens were 18 months of age. In the 12 hens on the ‘low-fat, low-cholesterol’ diet, the incidence and severity of atheromatosis was 25% and 5%, respectively; in the 12 on the ‘high-fat’ diet it was 75% and 25%, respectively. There was no difference in the incidence and severity of atheromatosis between the ‘layers’ and ‘nonlayers.’ Since egg laying is associated with a marked hyperlipemia and not a hypercholesterolemia, these results show also that a hyperlipemia alone though present for almost one year does not increase the rate of accumulation of cholesterol in the arteries of hens.

scholarly journals Olfactory Learning Supports an Adaptive Sugar-Aversion Gustatory Phenotype in the German Cockroach

Insects ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 724
Author(s):  
Ayako Wada-Katsumata ◽  
Coby Schal
Keyword(s):  
Food Preferences ◽  
Conditioning Session ◽  
Olfactory Learning ◽  
Food Sources ◽  
Olfactory Memory ◽  
Conditioning Paradigm ◽  
Foraging Decisions ◽  
Food Odors ◽  
Behavioral Resistance ◽  
Specific Food

An association of food sources with odors prominently guides foraging behavior in animals. To understand the interaction of olfactory memory and food preferences, we used glucose-averse (GA) German cockroaches. Multiple populations of cockroaches evolved a gustatory polymorphism where glucose is perceived as a deterrent and enables GA cockroaches to avoid eating glucose-containing toxic baits. Comparative behavioral analysis using an operant conditioning paradigm revealed that learning and memory guide foraging decisions. Cockroaches learned to associate specific food odors with fructose (phagostimulant, reward) within only a 1 h conditioning session, and with caffeine (deterrent, punishment) after only three 1 h conditioning sessions. Glucose acted as reward in wild type (WT) cockroaches, but GA cockroaches learned to avoid an innately attractive odor that was associated with glucose. Olfactory memory was retained for at least 3 days after three 1 h conditioning sessions. Our results reveal that specific tastants can serve as potent reward or punishment in olfactory associative learning, which reinforces gustatory food preferences. Olfactory learning, therefore, reinforces behavioral resistance of GA cockroaches to sugar-containing toxic baits. Cockroaches may also generalize their olfactory learning to baits that contain the same or similar attractive odors even if they do not contain glucose.

scholarly journals Olfactory Learning Supports an Adaptive Sugar-Aversion Gustatory Phenotype in the German Cockroach

2021 ◽  
Author(s):  
Ayako Wada-Katsumata ◽  
Coby Schal
Keyword(s):  
Food Preferences ◽  
Conditioning Session ◽  
Olfactory Learning ◽  
Food Sources ◽  
Olfactory Memory ◽  
Conditioning Paradigm ◽  
Foraging Decisions ◽  
Food Odors ◽  
Behavioral Resistance ◽  
Specific Food

An association of food sources with odors prominently guides foraging behavior in animals. To understand the interaction of olfactory memory and food preferences, we used glucose-averse (GA) German cockroaches. Multiple populations of cockroaches evolved a gustatory polymorphism where glucose is perceived as a deterrent and enables GA cockroaches to avoid eating glucose-containing toxic baits. Comparative behavioral analysis using an operant conditioning paradigm revealed that learning and memory guide foraging decisions. Cockroaches learned to associate specific food odors with fructose (phagostimulant, reward) within only a 1 hr conditioning session, and with caffeine (deterrent, punishment) after only three 1 hr conditioning sessions. Glucose acted as reward in wild type (WT) cockroaches, but GA cockroaches learned to avoid an innately attractive odor that was associated with glucose. Olfactory memory was retained for at least 3 days after three 1 hr conditioning sessions. Our results reveal that specific tastants can serve as potent reward or punishment in olfactory associative learning, which reinforces gustatory food preferences. Olfactory learning therefore reinforces behavioral resistance of GA cockroaches to sugar-containing toxic baits. Cockroaches may also generalize their olfactory learning to baits that contain the same or similar attractive odors even if they do not contain glucose.

Prospective Randomized Trial of Low-Saturated-Fat, Low-Cholesterol Diet During the First 3 Years of Life

Circulation ◽  
1996 ◽  
Vol 94 (6) ◽  
pp. 1386-1393 ◽  
Author(s):  
Harri Niinikoski ◽  
Jorma Viikari ◽  
Tapani Ro¨nnemaa ◽  
Helena Lapinleimu ◽  
Eero Jokinen ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Saturated Fat ◽  
Prospective Randomized Trial ◽  
Cholesterol Diet ◽  
Low Cholesterol

scholarly journals Regulation of Cholesterol Homeostasis by the Liver X Receptors in the Central Nervous System

2002 ◽  
Vol 16 (6) ◽  
pp. 1378-1385 ◽  
Author(s):  
Karl D. Whitney ◽  
Michael A. Watson ◽  
Jon L. Collins ◽  
William G. Benson ◽  
Tammy M. Stone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Cholesterol Efflux ◽  
Target Genes ◽  
Cholesterol Homeostasis ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures ◽  
The Central Nervous System ◽  
Lxr Agonists

Abstract The nuclear oxysterol receptors liver X receptor-α [LXRα (NR1H3)] and LXRβ (NR1H2) coordinately regulate genes involved in cholesterol homeostasis. Although both LXR subtypes are expressed in the brain, their roles in this tissue remain largely unexplored. In this report, we show that LXR agonists have marked effects on gene expression in murine brain tissue both in vitro and in vivo. In primary astrocyte cultures, LXR agonists regulated several established LXR target genes, including ATP binding cassette transporter A1, and enhanced cholesterol efflux. In contrast, little or no effect on gene expression or cholesterol efflux was detected in primary neuronal cultures. Treatment of mice with a selective LXR agonist resulted in the induction of several LXR target genes related to cholesterol homeostasis in the cerebellum and hippocampus. These data provide the first evidence that the LXRs regulate cholesterol homeostasis in the central nervous system. Because dysregulation of cholesterol balance is implicated in central nervous system diseases such as Alzheimer’s and Niemann-Pick disease, pharmacological manipulation of the LXRs may prove beneficial in the treatment of these disorders.

scholarly journals Increased circulating LDL cholesterol increases myeloma tumour burden in vivo

2021 ◽  
Vol 2 (4) ◽  
Author(s):  
Beatriz Gamez
Keyword(s):  
Bone Disease ◽  
Dietary Intervention ◽  
Dietary Cholesterol ◽  
Cholesterol Diet ◽  
Tumour Burden ◽  
Benign Condition ◽  
Myeloma Cells ◽  
Osteolytic Bone Disease

Gámez B., Morris EV., Olechnowicz S., Sowman, A., Turner, C. and Edwards CM.   Multiple myeloma (MM) is a fatal malignancy characterized by an expansion of malignant plasma cells in the bone marrow (BM) and associated with osteolytic bone disease. MM is preceded by the benign condition, monoclonal gammopathy of undetermined significance (MGUS). Understanding MGUS progression and development of MM bone disease is key for patient management. We and others have previously demonstrated that diet-induced obesity promotes myeloma progression, but the mechanisms underlying this remain unknown. The aim of the current study was to determine the effect of dietary cholesterol on MM development. A 2% cholesterol diet was used to increase circulating LDL in mice. Mice were randomly distributed to either a) cholesterol diet 4 weeks prior to 5TGM1 MM inoculation (pretreatment) or b) cholesterol diet 4 weeks prior to MM inoculation and continued for the entire experiment (continuous). Mice on the continuous cholesterol diet had increased tumour burden, associated with an increase in lipid droplet content of MM cells. No differences in tumour burden were seen in those mice where cholesterol diet was halted at time of MM inoculation. In vitro, myeloma cells cultured with delipidated FBS had a 50% reduction in viability after 72 hours. Rich cholesterol content lipoproteins (LDL) but not VLDL could restore MM cell viability, suggesting that cholesterol is responsible for this lipid-depletion effect. Taken together, our results show that high cholesterol promotes myeloma and results in a higher lipid content in myeloma cells, ultimately increasing BM tumour burden. Pretreatment with a cholesterol diet did not alter disease progression suggesting a direct pro-tumourigenic effect of cholesterol. These results demonstrate both the detrimental effect of cholesterol on myeloma progression and the potential for dietary intervention approaches.

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