Guy Hollifield

METABOLIC ADAPTATIONS TO A “STUFF AND STARVE” FEEDING PROGRAM. II. OBESITY AND THE PERSISTENCE OF ADAPTIVE CHANGES IN ADIPOSE TISSUE AND LIVER OCCURRING IN RATS LIMITED TO A SHORT DAILY FEEDING PERIOD

Many obese people who want to lose weight seem unable to follow diets which will allow them to achieve and maintain ideal weight (1-3). This failure to follow diets has been ascribed to a lack of interest or to psychological factors, since no clear-cut abnormality in so-called simple or exogenous obesity other than excessive food intake has been delineated (4). However, many obese patients consume most of their food within a relatively short period each day (5), and an interest in this unusual eating pattern prompted a study of rats allowed access to more food than they were able to consume for periods of up to 7 days. These studies (6) showed that adipose tissue from these animals developed a very remarkable ability to incorporate large amounts of acetate-l-CI4 into lipids in vitro after 5 days on this program. This increase in acetate incorporation into lipids is accompanied by striking increases in glucose-6phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activity in adipose tissue homogenates. Liver glycogen in animals fasted for 24 hours after being allowed food for only 2 hours per day, for 4 or 5 days, was much higher than it was in rats fed ad libitum after a similar fast. These observations have prompted the present investigations in which we have studied the effects, over a longer period of time, of this type of feeding program on body weight of rats, and have attempted to learn how long these adaptive changes persist when the animals are again allowed food ad libitum.

A STUDY OF THE RATE OF PROTEIN SYNTHESIS BEFORE AND DURING THE ADMINISTRATION OF L-TRIIODOTHYRONINE TO PATIENTS WITH MYXEDEMA AND HEALTHY VOLUNTEERS USING N-15 GLYCINE

The purpose of this paper is to report studies of the protein synthesis rate and the size of the metabolic pool using the amino acid, glycine labeled with isotopic nitrogen N-15. Employing the technique described by San Pietro and Rittenberg (1) studies were made on six patients with primary myxedema, four of them before and during the administration of l-triiodothyronine.2 Five healthy volunteers, one of whom received 1-triiodothyronine, are also included in this report. The N-15 glycine method used in this study is based upon the assumptions that dietary amino acids interact with tissue constituents at a rapid rate (2) and that a dietary amino acid either is used for protein synthesis or is oxidized and its nitrogen excreted. Figure 1, modified from San Pietro and Rittenberg, illustrates the technique. The metabolic pool (P) is defined as the mixture of nitrogenous compounds derived from the diet and from the breakdown of tissues. Dietary nitrogen enters this pool where part of it is used for protein synthesis. Another part is converted to urea, mixes with the urea already present and is excreted in the urine. The small amount of non-urea nitrogen can be disregarded. The total urea in the body constitutes the urea pool. For the steady

Addison's disease associated with histoplasmosis:Report of four cases and review of the literature

Abstract 1.1. Four cases of Addisons disease associated with proved histoplasmosis are reported. Three of the patients are alive and in fair health five years, three years and three months, respectively, after the diagnosis of the two diseases had been established. The autopsy of the fourth case revealed destruction of the adrenal glands by caseation necrosis. The necrotic material contained H. capsulatum. 2.2. Two of the four cases reported were first diagnosed as sarcoidosis on the basis of lymph node biopsy. 3.3. Histoplasmosis should be considered as an etiologic agent in Addisons disease as suggested by these cases and by a review of 103 cases of histoplasmosis in which 35 per cent of the cases were found to have adrenal involvement. This is a higher incidence of adrenal involvement than in the other systemic mycoses.

The effects of caffeine, deoxyribose nucleic acid and insulin on the metabolism of glucose by adipose tissue in vitro☆

Abstract The main effects and interactions of caffeine, DNA and insulin have been studied in the isolated rat epididymal fat pad, utilizing a 2 3 factorial design, with balanced segments from 5 groups of 4 rats each. The results were evaluated by analysis of variance. Insulin has the expected stimulatory effect, DNA no effect, and caffeine an inhibitory effect on C 14 O 2 production and C 14 lipid incorporation from glucose-1-C 14 in a Krebs bicarbonate buffer. Both DNA and insulin were significantly antagonistic to caffeine in this system, and this was also true of DNA and insulin together in the presence of caffeine. Possible explanations and significance of these findings are discussed.

Clinical studyAddison's disease associated with histoplasmosis: Report of four cases and review of the literature

Abstract 1.1. Four cases of Addisons disease associated with proved histoplasmosis are reported. Three of the patients are alive and in fair health five years, three years and three months, respectively, after the diagnosis of the two diseases had been established. The autopsy of the fourth case revealed destruction of the adrenal glands by caseation necrosis. The necrotic material contained H. capsulatum. 2.2. Two of the four cases reported were first diagnosed as sarcoidosis on the basis of lymph node biopsy. 3.3. Histoplasmosis should be considered as an etiologic agent in Addisons disease as suggested by these cases and by a review of 103 cases of histoplasmosis in which 35 per cent of the cases were found to have adrenal involvement. This is a higher incidence of adrenal involvement than in the other systemic mycoses.

Response of human adipose tissue to endogenous serum insulin-like activity in vitro

Abstract Human adipose tissue, obtained by subcutaneous biopsy from 18 normal and 22 diabetic adult subjects, was incubated with beef insulin or serum from the same donor; rat adipose tissue was similarly studied. Oxidation of glucose-1-C 14 to C 14 O 2 was minimal in buffer, increasing significantly with the addition of 31 μU/ml. and 500 μU/ml. of beef insulin. Serum ILA did not produce a comparable increase in oxidation. Addition of NADPH in vitro increased oxidation by human adipose tissue and depressed oxidation by rat epididymal tissue. When glucose-stimulated ILA and tolbutamide-stimulated ILA from the same subject were incubated with his own adipose tissue, the ranking of ILA levels agreed with that of rat adipose tissue in the case of nondiabetic subjects but correlated in only a random fashion when diabetic subjects were tested. Human adipose tissue exhibits both qualitative and quantitative differences from rat adipose tissue, and its clinical role in health and disease cannot always be predicted by study of the animal counterpart.

The effects of starvation and refeeding on hexosemonophosphate shunt enzyme activity and DNA, RNA, and nitrogen content of rat adipose tissue

Abstract The activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconic dehydrogenase (6PGD), and the RNA, DNA, and nitrogen content of rat adipose tissue have been estimated during periods of starvation and refeeding. The activities of the enzymes fall on starvation and rise on refeeding, and the RNA content of the fat shows a similar pattern. There is no change in DNA content and adipose tissue nitrogen rises on starvation, remaining high after refeeding has been commenced following a 9-day fast. These data are interpreted as being consistent with the idea that the changes in enzyme activity observed are directly related to changes in protein synthesis in adipose tissue, and reflect atrophy and resynthesis of enzymes during the period studied.

Glucose-6-phosphate dehydrogenase activity in adipose tissue from two types of obese mice during starvation☆

Abstract The activity of the enzyme glucose-6-phosphate dehydrogenase (G6PD) has been studied in congenital obese hyperglycemic (Obob) and gold thioglucose obese mice (GTO) and appropriate controls during periods of starvation. Obob mice show no fall in enzyme activity during starvation, an observation in keeping with the fact that the rate of lipogenesis remains high in these animals on starvation. GTO mice show a significant fall in enzyme activity by 24 hours of fasting, the level remaining low thereafter. After an initial fall in enzyme activity at 12 hours, normal Ob control and DBA 2 J mice show an apparent rise in enzyme activity at 24 hours followed by a secondary fall, and it is theorized that this rise in activity may represent a gluconeogenetic adaptive mechanism to starvation.

Alterations of protein metabolism in myxedema.

W I’IYH the exception of the reduction in total energy exchange, perhaps the most conspicuous alteration in the athyrotic state is that in protein metabolism.“’ This statement by Means clearly poses the problem which is the subject of this presentation. Protein abnormalities in myxedematous patients have interested investigators for some time, and it is the purpose of this communication to summarize some of these studies. An attempt will be made to correlate studies from our laboratory with those in the literature in an effort to formulate a working concept of abnormalities of protein metabolism in patients with myxedema. Experimental investigations in animals which apply to this problem will also be reviewed.

Selective mobilization of fatty acids from the adipose tissue of obese hyperglycemic mice

Abstract The fatty acid composition of the triglycerides of the fat pad has been determined in normal and obese hyperglycemic mice. After starvation the fat pad triglyceride of normal mice showed a significant rise in the proportion of oleic acid, and no change in the proportion of linoleic acid. In contrast, starved obese hyperglycemic mice showed no change in oleic acid and a significant increase in linoleic acid. Preliminary evidence is presented for a mechanism whereby linoleic acid might be retained due to decreased activity of monoglyceride lipase and recycled back to triglyceride in the adipose tissue of obese hyperglycemic mice during starvation.