Testosterone protects against early atherogenesis by beneficially modulating tissue-specific metabolic function in liver, muscle and adipose of male mice

It is clear that insulin-like growth factor-1 (IGF1) is important in supporting growth and regulating metabolism. The IGF1 found in the circulation is primarily produced by the liver hepatocytes, but healthy mature hepatocytes do not express appreciable levels of the IGF1 receptor (IGF1R). Therefore, the metabolic actions of IGF1 are thought to be mediated via extra-hepatocyte actions. Given the structural and functional homology between IGF1/IGF1R and insulin receptor (INSR) signaling, and the fact that IGF1, IGF1R and INSR are expressed in most tissues of the body, it is difficult to separate out the tissue-specific contributions of IGF1/IGF1R in maintaining whole body metabolic function. To circumvent this problem, over the last 20 years, investigators have taken advantage of the Cre/loxP system to manipulate IGF1/IGF1R in a tissue-dependent, and more recently, an age-dependent fashion. These studies have revealed that IGF1/IGF1R can alter extra-hepatocyte function to regulate hormonal inputs to the liver and/or alter tissue-specific carbohydrate and lipid metabolism to alter nutrient flux to liver, where these actions are not mutually exclusive, but serve to integrate the function of all tissues to support the metabolic needs of the organism.

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Chronological Aging Standard Curves of Telomere Length and Mitochondrial DNA Copy Number in Twelve Tissues of C57BL/6 Male Mouse

Cells ◽

10.3390/cells8030247 ◽

2019 ◽

Vol 8 (3) ◽

pp. 247 ◽

Cited By ~ 11

Author(s):

Ji Baek ◽

Hyeonwi Son ◽

Young-Hoon Jeong ◽

Sang Park ◽

Hyun Kim

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Dna ◽

Telomere Length ◽

Copy Number ◽

Accelerated Aging ◽

Male Mice ◽

Dna Copy Number ◽

Tissue Specific ◽

Chronological Aging ◽

Mitochondrial Dna Copy Number

The changes in telomere length and mitochondrial DNA copy number (mtDNAcn) are considered to be aging markers. However, many studies have provided contradictory or only fragmentary information about changes of these markers in animal models, due to inaccurate analysis methods and a lack of objective aging standards. To establish chronological aging standards for these two markers, we analyzed telomere length and mtDNAcn in 12 tissues—leukocytes, prefrontal cortex, hippocampus, pituitary gland, adrenal gland, retina, aorta, liver, kidney, spleen, skeletal muscle, and skin—from a commonly used rodent model, C57BL/6 male mice aged 2–24 months. It was found that at least one of the markers changed age-dependently in all tissues. In the leukocytes, hippocampus, retina, and skeletal muscle, both markers changed age-dependently. As a practical application, the aging marker changes were analyzed after chronic immobilization stress (CIS) to see whether CIS accelerated aging or not. The degree of tissue-aging was calculated using each standard curve and found that CIS accelerated aging in a tissue-specific manner. Therefore, it is expected that researchers can use our standard curves to objectively estimate tissue-specific aging accelerating effects of experimental conditions for least 12 tissues in C57BL/6 male mice.

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Chronic exposure to a pollutant mixture at low doses led to tissue-specific metabolic alterations in male mice fed standard and high-fat high-sucrose diet

Chemosphere ◽

10.1016/j.chemosphere.2018.12.177 ◽

2019 ◽

Vol 220 ◽

pp. 1187-1199 ◽

Cited By ~ 6

Author(s):

Danielle Naville ◽

Guillain Gaillard ◽

Benoit Julien ◽

Nathalie Vega ◽

Claudie Pinteur ◽

...

Keyword(s):

Chronic Exposure ◽

Low Doses ◽

Male Mice ◽

High Fat ◽

Tissue Specific ◽

Metabolic Alterations ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose

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Tissue-specific regulation of cytochrome P-450 dependent testosterone 15α-hydroxylase

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-118 ◽

1990 ◽

Vol 68 (6) ◽

pp. 769-776 ◽

Cited By ~ 12

Author(s):

E. James Squires ◽

Masahiko Negishi

Keyword(s):

Cdna Libraries ◽

Cdna Clones ◽

Type I ◽

Type Ii ◽

Male Mice ◽

Hydroxylase Activity ◽

Tissue Specific ◽

Liver And Kidney ◽

Kidney Microsomes ◽

Cytochrome P 450

Testosterone 15α-hydroxylase activity in kidney microsomes is higher in male mice than in female mice, while in the liver the activity is higher in females than in males. Cytochrome P-45Q15α, a specific form of cytochrome P-450 having testosterone 15α-hydroxylase activity, accounts for virtually all of the testosterone 15α-hydroxylase activity in female kidney microsomes, while other isozymes of testosterone 15α-hydroxylase are present in male kidney microsomes. In female kidney, P-45015α expression is regulated by a single sex-dependent locus, called Rsh for "regulation of steroid hydroxylase." The higher level of P-45015α expression in male kidneys is dependent on androgens. Of all mice strains, 129/J seems to be the least dependent on androgens to maintain a high expression of P-45015α in male kidneys. Castration of male mice lowers kidney levels of P-45015α but in the liver, P-45015α, levels rise after castration. This reciprocal regulation of P-45015α genes in liver and kidney was investigated by isolating cDNA clones encoding P-45015α from liver and kidney cDNA libraries. Two highly homologous cDNA clones encoding P-45015α designated type I and type II were identified, and levels of type I and type ÏI mRNA in liver and kidney were determined by differential restriction mapping of double-stranded cDNA prepared from mRNA from these tissues. Only type I mRNA is present in male kidney and only type II mRNA is present in female kidney, while both type I and type II mRNA are present in liver. Castration results in decreased levels of type I mRNA in male kidney but increased levels of type I mRNA in male liver. The levels of type II mRNA are not affected by androgens. We conclude that type I gene is induced in male kidneys and repressed in male liver by androgens, while type II gene expression is not affected by androgens.Key words: cytochrome P-450, 15α-hydroxylase, androgen-dependent expression, tissue-specific expression.

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Vehicle emissions-exposure alters expression of systemic and tissue-specific components of the renin-angiotensin system and promotes outcomes associated with cardiovascular disease and obesity in wild-type C57BL/6 male mice

Toxicology Reports ◽

10.1016/j.toxrep.2021.04.001 ◽

2021 ◽

Vol 8 ◽

pp. 846-862

Author(s):

Benjamin L. Phipps ◽

Usa Suwannasual ◽

JoAnn Lucero ◽

Nicholas A. Mitchell ◽

Amie K. Lund

Keyword(s):

Cardiovascular Disease ◽

Vehicle Emissions ◽

Renin Angiotensin System ◽

Male Mice ◽

Wild Type ◽

Angiotensin System ◽

Tissue Specific ◽

Renin Angiotensin

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Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner

Nature Communications ◽

10.1038/s41467-021-22001-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nazmin Bithi ◽

Christopher Link ◽

Yoko O. Henderson ◽

Suzie Kim ◽

Jie Yang ◽

...

Keyword(s):

Dietary Restriction ◽

Active Metabolite ◽

Dependent Manner ◽

Biological Processes ◽

Male Mice ◽

Tissue Protein ◽

Tissue Specific ◽

Redox Active ◽

Associated Functions ◽

Mammalian Protein

AbstractHydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSnH). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions and interventions known to modulate H2S production. We hypothesize that dietary restriction (DR), which increases lifespan and can boost H2S production, expands tissue-specific persulfidomes. Here, we find protein persulfidation enriched in liver, kidney, muscle, and brain but decreased in heart of young and aged male mice under two forms of DR, with DR promoting persulfidation in numerous metabolic and aging-related pathways. Mice lacking cystathionine γ-lyase (CGL) have overall decreased tissue protein persulfidation numbers and fail to functionally augment persulfidomes in response to DR, predominantly in kidney, muscle, and brain. Here, we define tissue- and CGL-dependent persulfidomes and how diet transforms their makeup, underscoring the breadth for DR and H2S to impact biological processes and organismal health.

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Ultrastructural Lesions Produced by Alcohol and Sucrose in the Heart and Liver of C57BL Mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100068035 ◽

1970 ◽

Vol 28 ◽

pp. 208-209

Author(s):

K.K. SEKHRI ◽

C.S. ALEXANDER ◽

H.T. NAGASAWA

Keyword(s):

Osmium Tetroxide ◽

Male Mice ◽

Alcohol Group ◽

Group Iii ◽

Group I ◽

C57bl Mice ◽

Group Ii

C57BL male mice (Jackson Lab., Bar Harbor, Maine) weighing about 18 gms were randomly divided into three groups: group I was fed sweetened liquid alcohol diet (modified Schenkl) in which 36% of the calories were derived from alcohol; group II was maintained on a similar diet but alcohol was isocalorically substituted by sucrose; group III was fed regular mouse chow ad lib for five months. Liver and heart tissues were fixed in 2.5% cacodylate buffered glutaraldehyde, post-fixed in 2% osmium tetroxide and embedded in Epon-araldite.

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