Edgar S. Gordon

Comparative aspects of lipogenesis in mammalian tissues

Abstract Human adipose tissue, unlike that of the rat, has a poor capacity to synthesize fatty acids de novo. The citrate cleavage enzyme is essentially absent from human adipose tissue, and other related lipogenic enzymatic activities are considerably lower and less adaptive than in rat epididymal fat. Studies carried out with monkey liver indicate, indirectly at least, a closer relationship of primate and rat liver. Comparison of lipogenesis in a number of animals indicates that the rat may be a poor experimental model to study the carbon pathway and regulation of lipogenesis.

Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus

Abstract Through the use of a double-blind cross-over investigative method, the effect of trivalent chromium supplements on blood sugar concentrations of normal and diabetic human subjects was evaluated. Four normal and 10 diabetic subjects took 50 μg. of trivalent chromium and a chromium-placebo thrice daily by mouth for 16-week periods. Chromium did not improve hyperglycemia in diabetic patients, and there was no difference in diabetic glucose tolerance measured after placebo and chromium treatment. Normal glucose tolerance was also unaffected. Despite evidence that trivalent chromium may be an essential micronutrient for maintenance of normal glucose tolerance in rats, results of this investigation do not support suggestions of a similar role in man.

Hypothyroidism After Low-Dose 131I Treatment of Hyperthyroidism

Abstract Sixty-four patients with hyperthyroidism were treated with a single dose of 3 mCi or less of131I before 1951. Nine were lost to follow-up shortly after treatment. The other 55 were found, ...

Evidence for a Sodium Retaining Factor in Toxemia of Pregnancy.

Summary A marked rise in excretion of a sodium retaining factor has been observed in toxemic pregnancies in both diabetic and non-diabetic patients. The increase has been observed in one patient before other toxemic symptoms have become evident. No parallel increases in 11-oxysteroid excretions were found in these patients.

Die physiologische Rolle des Fettgewebes

ZusammenfassungDas Fettgewebe stand in jüngerer Zeit aufgrund seiner hohen Aktivität im Kohlenhydrat- und Fettstoffwechsel im Mittelpunkt zahlreicher Forschungsarbeiten. Es wird versucht, die physiologische und biochemische Rolle des Fettgewebes zu umreißen. In einem Organismus, der auf eine diskontinuierliche Zufuhr von Nahrung eingestellt ist, muß ein Gewebe, dessen Spezialität die Speicherung und Mobilisierung von Energie ist, einen hervorragenden Platz im Stoffwechselgeschehen einnehmen. Insulin, das Hormon der Lipogenese par excellence, kontrolliert beide Vorgänge, die Speicherung und Mobilisierung von Fett, und verknüpft sie eng mit dem Stoffwechsel der Kohlenhydrate. Dies geschieht auf der einen Seite durch eine Steigerung der Glucoseverwertung und damit erhöhte Bildung von Acetyl-CoA und Co-Fermenten zur Fettsäuresynthese sowie von α-Glycerophosphat, das die Veresterung der Fettsäuren und ihre Deponierung als Triglyceride ermöglicht, auf der anderen Seite durch einen direkten hemmenden Einfluß auf das lipolytische System des Fettgewebes. Dem Insulin stehen zahlreiche Faktoren gegenüber, die eine Mobilisierung von Fettsäuren bewirken, wie das sympathische Nervensystem, Adrenalin und Noradrenalin, ACTH und das Wachstumshormon. Ein ausgewogenes Gleichgewicht von Fettsäureveresterung und -freigabe, das sich je nach Stoffwechsellage nach beiden Seiten verschieben läßt, ermöglicht es dem tierischen Organismus, sich an extreme Schwankungen der Energieversorgung und des Energiebedarfs zu adaptieren. Die biochemischen Grundlagen dafür werden ausführlich dargelegt und die Rolle der Fettsäuren im Energiehaushalt unterstrichen.Die Kenntnis dieser Stoffwechselzusammenhänge ermöglicht das Verständnis der verschiedensten Stoffwechselerkrankungen. Es werden besonders die Verhältnisse bei Fettsucht und Diabetes mellitus hervorgehoben und die Entstehung der diabetischen Ketoacidose beschrieben.SummaryIn recent years, the high activity of adipose tissue in fat and carbohydrate metabolism has been increasingly emphasized in scientific studies. It is conceivable that a tissue specialized in storage and release of energy-rich material will be of extreme importance to an organism adapted to discontinuous food supply. Both storage and mobilization of fat are under the immediate control of insulin, the hormone of lipogenesis par excellence, and are thus closely related to carbohydrate metabolism. Stimulation of glucose metabolism by insulin results in an increased formation of acetyl-CoA and of Co-factors necessary for fatty acid synthesis as well as of α-glycerophosphate for fatty acid esterification and deposition. Insulin also shows a direct inhibitory action on the lipolytic system of adipose tissue. There are, on the other hand, numerous factors promoting fatty acid mobilization, such as the sympathetic nervous system, epinephrine and norepinephrine, ACTH and growth hormone. A close equilibrium — which may be shifted into either direction to enable the organism to adapt to extreme changes in energy supply and energy need — has been established between fatty acid esterification and fatty acid release. The biochemical background of these regulations is discussed in detail and the role of fatty acids in energy metabolism is pointed out.The knowledge of these metabolic events is necessary to understand diseases related to fat metabolism, such as obesity, diabetes mellitus and the development of diabetic ketoacidosis.

Effect of a short period of cold exposure on plasma FFA level in lean and obese humans.

Abstract Plasma FFA level rose in normal weight control and to a lesser degree in obese women when they were exposed to cold at 4–6°C for a period of 30 minutes. This rise, in lean subjects, of plasma FFA was eliminated by pretreatment with either nicotinic acid or propranolol. The response to cold was a biphasic one with an early fall in plasma FFA level followed by a rise. The rise in plasma FFA appears to be catecholamine induced, and the absence of significant change in blood glucose would suggest that norepinephrine may be the stimulus. The biphasic nature of the response to cold suggests a favoring of utilization to mobilization of FFA early and the reverse later. The difference in the response noted in obese women may represent a decreased responsiveness, but possibly may be due to an insulating effect of adipose tissue mass.

Carbon-14 studies of energy metabolism in various thyroid states☆

Abstract Employing isotope equipment which produces a continuous recording of C14O2 specific activity in expired air, the oxidative patterns of palmitate-1-C14, acetate-1-C14, pyruvate-1-C14, glucose-1-C14 and glucose-6-C14 were studied in hyperthyroid, hyyothyroid and hypopituitary patients and compared with normal controls. Several patients were restudied following specific and non-specific treatments. A qualitative estimation of the proportion of glucose oxidation proceeding via the pentose “shunt” was obtained by comparing the oxidative patterns of C-1 versus C-6 labeled glucose-C14. Results indicate that hypothyroidism is characterized by a significant increase in the relative rates of C14-palmitate and acetate oxidation and a decrease in glucose oxidation, particularly in regard to pentose “shunt” activity. In contrast, patients with hyperthyroidism show a variable pattern of C14-palmitate and acetate oxidation, depending on the duration and severity of their disease, increased glucose oxidation and enhanced “shunt” activity. The latter is particularly evident in postmenopausal hyperthyroid females whose “shunt” activity is normally low. Whether or not the relationship between thyroid status and pentose “shunt” metabolism is due to a direct influence of thyroid hormones on glycolytic pathways or secondary to changes in either lipid turnover rates or estrogen metabolism remains speculative. Since the oxidative patterns of both C14-palmitate and acetate seem to reflect intracellular deficiency of thyroid hormone, these parameters can be utilized, within certain limitations, as a test of peripheral thyroid function. The striking “thyromimetic” effects of a DPN infusion, demonstrated in hypothyroid patients, and its lack of metabolic effect in normal controls, suggests that the cellular action of thyroid hormones may be mediated, in large measure, through changes in the ratio of oxidized to reduced DPN. Since C14-palmitate oxidation is within normal limits in patients with panhypopituitarism, this procedure can be a useful adjunct in differentiating primary from secondary thyroid failure in certain problem cases.

Enzyme Studies in Human Liver and Adipose Tissue

DURING an investigation of metabolic and hormonal control mechanisms in humans, a number of potentially adaptive enzymes in human liver and adipose tissue were investigated with regard to their possible regulatory function.

Evaluation of an epinephrine test in obesity

In 38 healthy normal weight controland 106 obese subjects measurements were made of serum PBI, fasting plasma free fatty acid (FFA) level and level of FFA 30 minutes after injecting 0.5 mg. aqueous epinephrine subcutaneously. Serum PBI level did not significantly differ in the groups suggesting independence from body weight. Fasting FFA level increased with weight, a finding not exlained by this study. The rise in FFA following epinephrine decreased as body weight increased. The proportion of control and obese subjects with a rise in FFA less than 300–400 μEq./L. was the same. It has been claimed that a diminished or absent response of FFA to a fixed subcutaneous dose of epinephrine defines a category of “metabolic” obesity. On the basis of this study it would appear that decreased response in a similar number of control and obese indicates the variation inherent in a test of this kind rather than a metabolic defect. The diminished response with increasing weight appears to reflect the response of larger subjects to a fixed dose of epinephrine rather than impaired mobilization of FFA.

Studies of energy metabolism in human subjects using carbon 14-labeled compounds: I. Effect of sex, state of nutrition and body weight

Abstract Employing isotope equipment which produces a continuous record of C 14 O 2 specific activity in expired air, the patterns of oxidation of a variety of intravenously administered C 14 -labeled compounds were studied in obese, malnourished and normal weight subjects of both sexes. C 14 O 2 specific activity curves derived from palmitate-1, acetate-1 and glucose-6-C 14 oxidation were similar in male and female control subjects; the rate and magnitude of glucose-1-C 14 oxidation, however, was considerably augmented in women with active ovarian function, when compared to the male or postmenopausal female patterns. Oxidation of all substrates to C 14 O 2 was markedly increased in malnourished patients while a significant suppression of glucose-6 and acetate-1-C 14 oxidation was noted in the majority of obese individuals. Attempts to correlate the respiratory data with various metabolic parameters were largely unsuccessful, except for a significant correlation between surface area and the magnitude of C 14 -acetate oxidation. The potential advantages and pitfalls of this method of studying intermediary energy metabolism in human subjects is discussed.