BackgroundKetosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets. However, the increasing interest on the ketogenic state has motivated the development of alternative approaches to rapidly increase ketonemia using less drastic interventions. Here, it was tested whether oral intake of a β-hydroxybutyrate (βHB) mineral salt mixture could increase ketonemia in Wistar rats without any other dietary changes, thereby being a useful model to study ketones effects alone on metabolism.MethodsβHB salts were orally administered to provoke elevation in the ketonemia. Effects of this intervention were tested acutely (by gavage) and chronically (4 weeks in drinking water). Acutely, a concomitant glucose overload was used to suppress endogenous ketogenesis and verify whether βHB salts were really absorbed or not. Long-term administration allowed to weekly evaluate the impact on ketonemia, blood glucose and, after 4 weeks, on body weight, visceral fat mass, lipid blood profile, serum lipolysis products and adiponectinemia.ResultsβHB salts increased ketonemia in acute and long-term administrations, improved blood lipid profile by raising HDL-cholesterol concentration and decreasing LDL/HDL ratio, while reduced visceral adipocyte volume. Mean ketonemia correlated positively with HDLc and negatively with adipocyte volume and serum lipolysis products.ConclusionsOral βHB can rapidly increase ketonemia and, therefore, be used as an acute and long-term animal model of ketosis. Long-term treatment points to important beneficial effects of ketone bodies in serum lipid concentrations and visceral fat mass. These results may help to explain the metabolic adaptations following ketogenic diets, such as a better body fat control and a serum lipid profile improvement.
Background:The Atkins diet program is a great example of the application of low carbohydrate diets for obesity, with the intention of weight loss and improvement in cardiovascular risk (CV risk). A good CV risk predictor is the atherogenic index of plasma (AIP) calculated as log (TG/HDL [mmol]), which is strongly affected by serum triglycerides, which in turn is associated with the carbohydrate intake. This study determined the effect of the initial phase of Atkins diet program, consisting in 20 g/day of carbohydrate intake with positive urinary ketones measure, in AIP of 12 adult overweight trained adapted men. The AIP was calculated before and after intervention. Results: After 14 days, BMI and triglycerides decreased significantly, while HDL-C increased. No alterations were described in LDL plasmatic concentration. Prior to the diet, 58.3% of subjects presented high CV risk and after 14 days of the diet program only 33.3% of subjects were classified as high CV risk, while more than 66% were low CV risk. The intervention was effective in 11 of 12 participants. However, in one person the dietary intervention increased AIP index. Conclusion: The initial phase of Atkins diet program could significantly decrease the AIP in 11 of 12 adult overweight trained adapted men. Dietary individual responses need to be more studied. Arch Endocrinol Metab. 2015;59(6):568-71
Little is known about adipocyte metabolism during aging process and whether this can influence body fat redistribution and systemic metabolism. To better understand this phenomenon, two animal groups were studied: young-14 weeks old-and middle-aged-16 months old. Periepididymal (PE) and subcutaneous (SC) adipocytes were isolated and tested for their capacities to perform lipolysis and to incorporate D-[U-(14)C]-glucose, D-[U-(14)C]-lactate, and [9,10(n)-(3)H]-oleic acid into lipids. Additionally, the morphometric characteristics of the adipose tissues, glucose tolerance tests, and biochemical determinations (fasting glucose, triglycerides, insulin) in blood were performed. The middle-aged rats showed adipocyte (PE and SC) hypertrophy and glucose intolerance, although there were no significant changes in fasting glycemia and insulin. Furthermore, PE tissue revealed elevated rates (+50 %) of lipolysis during beta-adrenergic-stimulation. There was also an increase (+62 %) in the baseline rate of glucose incorporation into lipids in the PE adipocytes, while these PE cells were almost unresponsive to insulin stimulation and less responsive (a 34 % decrease) in the SC tissue. Also, the capacity of oleic acid esterification was elevated in baseline state and with insulin stimulus in the PE tissue (+90 and 82 %, respectively). Likewise, spontaneous incorporation of lactate into lipids in the PE and SC tissues was higher (+100 and 11 %, respectively) in middle-aged rats. We concluded that adipocyte metabolism of middle-aged animals seems to strongly favor cellular hypertrophy and increased adipose mass, particularly the intra-abdominal PE fat pad. In discussion, we have interpreted all these results as a metabolic adaptations to avoid the spreading of fat that can reach tissues beyond adipose protecting them against ectopic fat accumulation. However, these adaptations may have the potential to lead to future metabolic dysfunctions seen in the senescence.
Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (−19% of maximal response and −60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (−19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients.
O grupo de Peter Arner (1), do conceituado Instituto Karolinska em Stockholm, Suécia, foi o primeiro a descrever um fenômeno denominado "resistência à lipólise". Essa resistência se caracteriza pela marcante diminuição da eficácia das catecolaminas em estimular a lipólise em adipócitos de pacientes com síndrome metabólica.A "resistência à lipólise" ocorre em consequência da menor capacidade de ativação da lipase sensível por hormônios (LHS) via AMPc, assim como pela combinação de múltiplos defeitos em vias adrenérgicas da mobilização dos lipídios, como a redução da expressão de receptores β-adrenérgicos. Tais dados foram confirmados e aprofundados em outras importantes publicações, nas quais também foi descrita menor expressão de lipases (2-4). Além disso, esses estudos estabeleceram correlações entre sensibilidade à insulina sistêmica e o número de receptores β 2 -adrenérgicos, bem como entre taxas máximas de lipólise e tolerância à glicose, demonstrando que quão menor a capacidade em realizar lipólise maior é o quadro de resistência à insulina e intolerância à glicose (1).Assim sendo, é razoável a hipótese de que, na síndrome metabólica, a dificuldade de mobilizar lipídios em adipócitos poderia, então, contribuir para o aumento da massa adiposa, agravando o quadro de obesidade e, consequentemente, reduzindo a sensibilidade à insulina.Entretanto, em trabalho recente (5) no qual participam Peter Arner e Dominique Langin, do Instituto de Doenças Metabólicas e Cardiovasculares da Universidade de Toulouse, França, o conhecimento da participação dos mecanismos de regulação da lipólise na obesidade e síndrome metabólica adquiriu uma nova temática.Segundo os autores, sabe-se que, em excesso, os ácidos graxos podem induzir resistência à ação da insulina. Neste estudo, a observação clínica da variação natural da lipólise (isto é, da lipólise não estimulada) em células de gordura de humanos revelou que a elevada taxa de lipólise basal está associada com baixa sensibilidade à insulina. Demonstrou-se, ainda, que a menor ação da enzima LHS, seja por modificações genéticas ou por inibição farmacológica, resulta em melhora da sensibilidade à insulina em ratos. Uma série de estudos em camundongos e em células de gordura humana demonstrou que, ao atenuar a capacidade lipolítica, a síntese de novos ácidos graxos a partir da glicose era ativada. Essa via metabólica foi recentemente proposta (6) como um dos principais determinantes da sensibilidade sistêmica à insulina.Tais dados levaram a crer que a inibição parcial da lipólise é uma estratégia plausível no tratamento da resistência à insulina associada à síndrome metabólica, o que parece paradoxal quando comparado aos trabalhos prévios do mesmo grupo. Nossa experiên-cia em metabolismo de adipócitos nos permite explicar esse aparente paradoxo.
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