The treatment of obesity by carbohydrate deprivation suppresses plasma tryptophan and its ratio to other large neutral amino acids

Héraïef, E; Burckhardt, P.; Mauron, C.; Wurtman, Judith J.; Wurtman, Richard J.

doi:10.1007/bf01245117

Cited by 18 publications

(4 citation statements)

References 17 publications

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“…While the majority of studies on BCAAs have focused on their roles in skeletal muscle, obesity-associated elevations in post-absorptive plasma levels of BCAAs had been observed in some early studies [12], [13], if not in all of them [14], [15]. An example of earlier evidence pointing to a role of adipose tissue in obesity-associated BCAA dysregulation comes from observations of reduced expression of mitochondrial branched-chain amino acid aminotransferase ( Bcat2 ) and branched-chain α-keto acid dehydrogenase ( Bckdha ) enzymes in epididymal fat from ob/ob mice and Zucker rats, compared to their lean counterparts [16].…”

Section: Introductionmentioning

confidence: 99%

Effects of Leucine Supplementation and Serum Withdrawal on Branched-Chain Amino Acid Pathway Gene and Protein Expression in Mouse Adipocytes

et al. 2014

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The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our understanding of the transcriptomic response of this pathway to variations in nutrient availability.

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Section: Introductionmentioning

confidence: 99%

Effects of Leucine Supplementation and Serum Withdrawal on Branched-Chain Amino Acid Pathway Gene and Protein Expression in Mouse Adipocytes

et al. 2014

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“…These data show that, in a heterogeneous group of obese outpatients, supplemental oral TRP, studied in a double-blind protocol, could enhance weight loss in some patients, and that potential responders could be identified, prospectively, based on the degree of initial obesity ("moderate"; 140-159% of IBW). Patients may have been especially responsive to TRP because they were concurrently on a reducing diet (PSMF) that can cause carbohydrate craving and that produces changes in the plasma amino acid pattern indicative of diminished brain serotonin synthesis (Heraief et al, 1983;Wurtman, 1982). However obesity per se apparently also reduces the "plasma TRP ratio" (Heraief et al, 1983), probably by increasing basal plasma levels of the branched-chain amino acids (Heraief et al, 1983) and decreasing their decline in response to insulin.…”

Section: Scu Sslonmentioning

confidence: 99%

“…twice daily) was lower than that generally used to induce sleep (Wyatt et al, 1970) or to treat depression (Coppen et al, 1967;Moller, Kirk, & Freming, 1976). A l-g dose, given at the same time as in the present study (1 hour after a meal), increased plasma TRP levels and the plasma TRP/LNAA ratio by 150-200% after 2 hours among subjects consuming a PSMF diet; however, the plasma TRP/LNAA ratio was not significantly elevated beyond that seen in the same subjects after an overnight fast while on a normal diet (Heraief et al, 1983). Most likely, much greater increases in the plasma TRP ratio would have been produced had we been able to give the TRP along with an insulin-releasing carbohydrate; the protocol of the PSMF diet precluded administering this combination.…”

Section: Scu Sslonmentioning

confidence: 99%

“…The carbohydrate cravings may, in these patients, be mediated by diet-induced changes in the plasma amino acid pattern, which secondarily diminish the synthesis and release of serotonin within the brain. Consuption of protein-rich, carbohydrate-poor meals lowers the "plasma/tryptophan (TRP) ratio" [the ratio of the TRP concentration to the summed concentration of other circulating large neutral amino acids (LNAA) which compete with TRP for passage across the blood-brain barrier (Crandall & Fernstrom, 1980;Fernstrom and Wurtman, 1971; Fernstrom, Larin, & Wurtman, 1973;Fernstrom et al, 1979;Wurtman, 1982)] well beyond its normal range (Heraief, Burckhardt, Mauron, Wurtman, & Wurtman, 1983), thereby diminishing the amounts of TRP available within brain neurons for conversion to serotonin. In our experience, the carbohydrate craving associated with the PSMF diet restricts this diets's overall success.…”

Section: Introductionmentioning

confidence: 99%

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Tryptophan administration may enhance weight loss by some moderately obese patients on a protein-sparing modified fast (PSMF) diet

Héraïef

Burckhardt

Wurtman

et al. 1985

Int. J. Eat. Disord.

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Drugs thought to enhance serotonin‐mediated neurotransmission have been shown to diminish appetite for carbohydrates. Therefore, we examined the ability of tryptophan (TRP), serotonin's amino acid precursor, or a placebo to influence weight loss among 62 obese Swiss outpatients who were on a reducing diet [the Protein‐Sparing Modified Fast (PSMF) Diet] which can be associated with severe carbohydrate craving. This diet provides relatively large amounts of protein (1.2–1.4 g/kg ideal body weight/day) but little carbohydrate (40 g/day or less), thus stimulating ketone body production. Its consumption also reduces the ratio of plasma TRP to the summed concentrations of the other large neutral amino acids, thereby probably diminishing brain TRP and serotonin levels. During the initial month of the PSMF diet all patients received the placebo; thereafter 30 received TRP (750 mg, twice daily, orally, for 3 months) and 32 the placebo, according to a double‐blind protocol. Among moderately obese patients (140–159% of ideal weight; n = 25), the TRP significantly enhanced weight loss (p lt;.05), especially during the first treatment month (3.4 ± 2.8 vs 7.7 ± 1.7 kg lost; means ± standard deviation) but also during the total 3‐month test period (2.6 ± 2.3 vs 1.5 ± 1.6 kg lost/month). The JRP didn't modify the reported adherence to the PSMF diet. The partial efficacy of TRP among our moderately obese subjects does not presently justify its routine use as an adjunct to a PSMF diet. However, greater efficacy may be obtained with better patient selection and under metabolic conditions designed to amplify the uptake of TRP into the brain (i.e., administration along with a carbohydrate).

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Responses to Carbohydrate Consumption Among Insulin-Dependent Diabetics

Spring

Bourgeois

Harden

et al. 1988

Dietary Phenylalanine and Brain Function

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The treatment of obesity by carbohydrate deprivation suppresses plasma tryptophan and its ratio to other large neutral amino acids

Cited by 18 publications

References 17 publications

Effects of Leucine Supplementation and Serum Withdrawal on Branched-Chain Amino Acid Pathway Gene and Protein Expression in Mouse Adipocytes

Effects of Leucine Supplementation and Serum Withdrawal on Branched-Chain Amino Acid Pathway Gene and Protein Expression in Mouse Adipocytes

Tryptophan administration may enhance weight loss by some moderately obese patients on a protein-sparing modified fast (PSMF) diet

Responses to Carbohydrate Consumption Among Insulin-Dependent Diabetics

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