scholarly journals Male castration alters the gut microbiota, leading to increased serum levels of branched-chain amino acids and adiposity

2019 ◽  
Author(s):  
Tae Woong Whon ◽  
Hyun Sik Kim ◽  
Na-Ri Shin ◽  
Eun Sung Jung ◽  
Euon Jung Tak ◽  
...  

Abstract Background: Testosterone deficiency is positively correlated with fat accumulation and obesity-related comorbidities, such as metabolic syndrome. Castration of young males is widely used in the cattle industry to improve meat quality. However, the mechanism linking hypogonadism and host metabolism is not clear. We aimed to evaluate the effect of male hypogonadism on the gut microbiota and serum metabolites, and the contribution of the altered microbiota to the host metabolic phenotype during hypogonadism. Results: We used metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. We then used a male mouse castration model to evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. After pubescence, the CtM cattle harbored distinct ileal microbiota dominated by the family Peptostreptococcaceae, and exhibited distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. Castration of male mice phenocopied both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model further revealed that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals. Conclusions: We demonstrated altered gut microbial profiles in the hypogonadal animals, with a negative feedback between the serum testosterone levels and the ileal abundance of Peptostreptococcaceae, and a distinct metabolic phenotype, with an enhanced amino acid metabolism. These findings suggest targeting the gut microbiota as a potential therapeutic strategy for the treatment of both hypogonadism and obesity.

2020 ◽  
Author(s):  
Tae Woong Whon ◽  
Hyun Sik Kim ◽  
Na-Ri Shin ◽  
Eun Sung Jung ◽  
Euon Jung Tak ◽  
...  

Abstract Background : Testosterone deficiency is positively correlated with fat accumulation and obesity-related comorbidities, such as metabolic syndrome. Castration of young males is widely used in the cattle industry to improve meat quality. However, the mechanism linking hypogonadism and host metabolism is not clear. We aimed to evaluate the effect of male hypogonadism on the gut microbiota and serum metabolites, and the contribution of the altered microbiota to the host metabolic phenotype during hypogonadism.Results : We used metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. We then used a male mouse castration model to evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. After pubescence, the CtM cattle harbored distinct ileal microbiota dominated by the family Peptostreptococcaceae , and exhibited distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. Castration of male mice phenocopied both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model further revealed that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals.Conclusions : We demonstrated altered gut microbial profiles in the hypogonadal animals, with a negative feedback between the serum testosterone levels and the ileal abundance of Peptostreptococcaceae , and a distinct metabolic phenotype, with an enhanced amino acid metabolism. These findings suggest targeting the gut microbiota as a potential therapeutic strategy for the treatment of both hypogonadism and obesity.


1986 ◽  
Vol 250 (4) ◽  
pp. E407-E413 ◽  
Author(s):  
R. A. Gelfand ◽  
M. G. Glickman ◽  
R. Jacob ◽  
R. S. Sherwin ◽  
R. A. DeFronzo

To compare the contributions of splanchnic and skeletal muscle tissues to the disposal of intravenously administered amino acids, regional amino acid exchange was measured across the splanchnic bed and leg in 11 normal volunteers. Postabsorptively, net release of amino acids by leg (largely alanine and glutamine) was complemented by the net splanchnic uptake of amino acids. Amino acid infusion via peripheral vein (0.2 g X kg-1 X h-1) caused a doubling of plasma insulin and glucagon levels and a threefold rise in blood amino acid concentrations. Both splanchnic and leg tissues showed significant uptake of infused amino acids. Splanchnic tissues accounted for approximately 70% of the total body amino acid nitrogen disposal; splanchnic uptake was greatest for the glucogenic amino acids but also included significant quantities of branched-chain amino acids. In contrast, leg amino acid uptake was dominated by the branched-chain amino acids. Based on the measured leg balance, body skeletal muscle was estimated to remove approximately 25-30% of the total infused amino acid load and approximately 65-70% of the infused branched-chain amino acids. Amino acid infusion significantly stimulated both the leg efflux and the splanchnic uptake of glutamine (not contained in the infusate). We conclude that when amino acids are infused peripherally in normal humans, splanchnic viscera (liver and gut) are the major sites of amino acid disposal.


1983 ◽  
Vol 244 (2) ◽  
pp. E151-E158 ◽  
Author(s):  
J. T. Brosnan ◽  
K. C. Man ◽  
D. E. Hall ◽  
S. A. Colbourne ◽  
M. E. Brosnan

Amino acid concentrations in whole blood, liver, kidney, skeletal muscle, and brain were measured and arteriovenous differences calculated for head, hindlimb, kidney, gut, and liver in control and streptozotocin-diabetic rats. In the control rats, glutamine was released by muscle and utilized by intestine, intestine released citrulline and alanine, liver removed alanine, and the kidneys removed glycine and produced serine. In diabetic rats, the major changes from the pattern of fluxes seen in the normal rat were the release of many amino acids from muscle, with glutamine and alanine predominating, and the uptake of these amino acids by the liver. Glutamine removal by the intestine was suppressed in diabetes, but a large renal uptake of glutamine was evident. Branched-chain amino acids were removed by the diabetic brain, and consequently, brain levels of a number of large neutral amino acids were decreased in diabetes.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Karin Shimada ◽  
Isao Matsui ◽  
Kazunori Inoue ◽  
Ayumi Matsumoto ◽  
Seiichi Yasuda ◽  
...  

Abstract Dietary phosphate intake is closely correlated with protein intake. However, the effects of the latter on phosphate-induced organ injuries remain uncertain. Herein, we investigated the effects of low (10.8%), moderate (23.0%), and high (35.2%) dietary casein and egg albumin administration on phosphate-induced organ injuries in rats. The moderate and high casein levels suppressed renal tubulointerstitial fibrosis and maintained mitochondrial integrity in the kidney. The serum creatinine levels were suppressed only in the high casein group. Phosphate-induced muscle weakness was also ameliorated by high dietary casein. The urinary and fecal phosphate levels in the early experiment stage showed that dietary casein did not affect phosphate absorption from the intestine. High dietary egg albumin showed similar kidney protective effects, while the egg albumin effects on muscle weakness were only marginally significant. As the plasma branched-chain amino acid levels were elevated in casein- and egg albumin-fed rats, we analyzed their effects. Dietary supplementation of 10% branched-chain amino acids suppressed phosphate-induced kidney injury and muscle weakness. Although dietary protein restriction is recommended in cases of chronic kidney disease, our findings indicate that the dietary casein, egg albumin, and branched-chain amino acid effects might be reconsidered in the era of a phosphate-enriched diet.


2015 ◽  
Vol 7 (4) ◽  
pp. 153-162 ◽  
Author(s):  
Jana Kazandjieva ◽  
Dimitrina Guleva ◽  
Assia Nikolova ◽  
Sonya Márina

Abstract Leucinosis (maple syrup urine disease - MSUD) is an inherited aminoacidopathy and organic aciduria caused by severe enzyme defect in the metabolic pathway of amino acids: leucine, isoleucine, and valine. The classical variant of the disease is characterized by accumulation of both amino and α-keto acids, particulary the most toxic rapid elevation of circulating leucine and its ketoacid, α-ketoisocaproate, which cause encephalopathy and life-threatening brain swelling. However, patients with the most severe form, classical maple syrup urine disease, may appear normal at birth, but develop acute metabolic decompensation within the first weeks of life with typical symptoms: poor feeding, vomiting, poor weight gain, somnolence and burnt sugar-smelling urine, reminiscent of maple syrup. Early diagnosis and dietary intervention improve the patient’s condition, prevent severe complications, and may allow normal intellectual development. We present a 4-month old infant with leucinosis dignosed 3 months earlier, due to elevated levels of amino acids: leucine, isoleucine and valine. The patient was full-term neonate with an uncomplecated delivery, without any family history of metabolic disorder or consanguinity. The infant was referred to a dermatologist, because of maculopapular exanthema on the scalp, trunk, upper and lower extremities, and exfoliative dermatitis of the perioral, particularly anogenital regions, associated with diarrhea. Skin involvement was associated with poor general condition of the infant exhibiting severe hypotension, anemic syndrome, dyspepsia and neurological symptoms. Exanthema developed a few days after the initiation of nutritional therapy for MSUD: isoleucine-, leucine-, and valine-free powdered medical food (MSUD-2) supplemented with iron. Zink levels were within normal ranges. Rapid skin improvement occurred after adequate branched-chain amino acids supplementation was commenced under regular laboratory control (normal zinc serum level with deficiencies of leucine and valine), skin hygiene with antiseptics, emollients and low potent topical corticosteroids. Treatment of acute metabolic decompensation and dietary restriction of branched-chain amino acids are the main aspects in the management of maple syrup urine disease. Common findings in patients with MSUD include: plasma amino acid imbalance, particularly of essential amino acids, failure to thrive attributed to restriction of particular precursor amino acids and natural proteins, micronutrient deficiencies or higher energy requirement due to chronic illness or inflammation. Due to low intake of branched-chain amino acids, some patients develop skin lesions known as acrodermatitis enteropathica-like syndrome. Here we report a case of an infant who developed acrodermatitis enteropathica-like skin eruptions due to branched-chain amino acid deficiency during treatment of maple syrup urine disease. According to available world literature, this is the first report of acrodermatitis enteropathica-like syndrome in an infant with maple syrup urine disease (leucinosis) in the Republic of Bulgaria.


1988 ◽  
Vol 254 (2) ◽  
pp. 579-584 ◽  
Author(s):  
P J Garlick ◽  
I Grant

Rates of muscle protein synthesis were measured in vivo in tissues of post-absorptive young rats that were given intravenous infusions of various combinations of insulin and amino acids. In the absence of amino acid infusion, there was a steady rise in muscle protein synthesis with plasma insulin concentration up to 158 mu units/ml, but when a complete amino acids mixtures was included maximal rates were obtained at 20 mu units/ml. The effect of the complete mixture could be reproduced by a mixture of essential amino acids or of branched-chain amino acids, but not by a non-essential mixture, alanine, methionine or glutamine. It is concluded that amino acids, particularly the branched-chain ones, increase the sensitivity of muscle protein synthesis to insulin.


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