Background and Methods. Some obese subjects repeatedly fail to lose weight even though they report restricting their caloric intake to less than 1200 kcal per day. We studied two explanations for this apparent resistance to diet — low total energy expenditure and underreporting of caloric intake — in 224 consecutive obese subjects presenting for treatment. Group 1 consisted of nine women and one man with a history of diet resistance in whom we evaluated total energy expenditure and its main thermogenic components and actual energy intake for 14 days by indirect calorimetry and analysis of body composition. Group 2, subgroups of which served as controls in the various evaluations, consisted of 67 women and 13 men with no history of diet resistance. Results. Total energy expenditure and resting metabolic rate in the subjects with diet resistance (group 1) were within 5 percent of the predicted values for body composition, and there was no significant difference between groups 1 and 2 in the thermic...

https://www.nejm.org/doi/pdf/10.1056/NEJM199212313272701

Discrepancy between Self-Reported and Actual Caloric Intake and Exercise in Obese Subjects

Prader-Willi syndrome is a complex disorder affecting multiple systems with many manifestations relating to hypothalamic insufficiency. Major findings include infantile hypotonia, developmental delay and mental retardation, behaviour disorder, characteristic facial appearance, obesity, hypogonadism, and short stature. Obesity and the behavioural problems are the major causes of morbidity and mortality. Prader-Willi syndrome is caused by abnormalities of the imprinted region of proximal 15q and results from absence of the normally active paternal genes in this region. Such absence results from paternal interstitial deletion, maternal uniparental disomy, or a mutation or other abnormality in the imprinting process. Diagnostic identification of all causes has become available in recent years, permitting early detection and institution of appropriate management. This testing has permitted recent identification of some phenotypic differences among affected subjects of different race and between those with deletions and uniparental disomy as a cause.

https://jmg.bmj.com/content/jmedgenet/34/11/917.full.pdf

Prader-Willi syndrome.

Estimates of the quantitative contribution of adipose tissue to whole-body glucose metabolism, previously reported as 1-3%, have been revised to be on the order of 10-30%. These revised estimates come, in part, from a recognition that adipose tissue uses glucose to produce lactate and pyruvate, in addition to CO2 and triglycerides. Lactate production by adipose tissue is modulated in vitro by changes in glucose, insulin, and epinephrine concentrations. In vivo, lactate production is regulated acutely by the animal's nutritional state (fed or fasted) and chronically by the degree of obesity. A strong positive correlation exists between rat fat cell size and relative conversion of glucose to lactate (r = 0.89, P less than 0.001). Diabetes is also associated with markedly increased lactate production in adipocytes. Fat cells from obese or diabetic rats (or humans) can metabolize to lactate as much as 50-70% of the glucose taken up. From these recent studies, a picture is emerging in which the adipose organ may provide lactate for hepatic gluconeogenesis during fasting, and also lactate for hepatic glycogen synthesis after food ingestion. Modulation of adipocyte lactate production and contribution of adipose tissue lactate to the body's fuel economy in physiological and pathological states are the focus of this review.

Lactate production in adipose tissue : a regulated function with extra-adipose implications

OBJECTIVE: To study the effect of diet composition on diet-induced thermogenesis (DIT) over 24 h in a respiration chamber. SUBJECTS: Eight healthy female volunteers (age 27±3 y; body mass index, BMI 23±3 kg/m2). DIETS: A high protein and carbohydrate (HP/C) (60:10:30; percentage energy (E%)carbohydrate, fat and protein, respectively) and high fat (HF) (30:60:10 respectively) diet, both isoenergetic, isovolumetric, composed of normal food items and matched for organoleptic properties (taste, smell, appearance). DESIGN: Subjects spent two 36 h periods each in a respiration chamber consuming both test diets in random order. Components of 24 h energy expenditure (24 h EE): sleeping metabolic rate, DIT and activity induced energy expenditure were measured. RESULTS: DIT was higher in all subjects while on the HP/C diet (1295 kJ/d vs 931 kJ/d; 14.6% vs 10.5% of energy intake; P<0.02). There was no significant difference in other components or total 24 h EE, although there was a trend towards higher EE on the HP/C diet. CONCLUSION: A high protein and carbohydrate diet induces a greater thermic response in healthy individuals when compared to a high fat diet.

Diet induced thermogenesis measured over 24h in a respiration chamber: effect of diet composition.

Lactate metabolism is altered in obesity Increasing obesity is associated with increased blood lactate levels after an overnight fast In contrast, we have recently shown a marked decrease in the capacity for acute lactate generation in obese subjects following an oral glucose load, which we postulated might be linked to altered insulin sensitivity In the present study, we systematically analyzed the relationship between insulin sensitivity (the Sensitivity Index [SI] derived using the minimal model), body mass index (BMI), and glucose, insulin, and lactate levels in the basal state and following intravenous (IV) glucose and insulin administration in lean and obese subjects The results showed that SI and BMI were inversely related, as expected Insulin sensitivity was more tightly associated with glucose, insulin, and lactate levels (both basal and integrated) than obesity per se A significant inverse relationship was found between SI and basal lactate levels (r = -56) Moreover, a significant and positive relationship was found between SI and incremental lactate area under the curve (reflecting acute lactate production) (r = 41) In a multiple regression analysis to separate the independent effects of obesity (BMI) and insulin sensitivity, after adjusting for age, sex, and race, SI accounted for 34% of the variance in basal lactate and 24% of the variance in incremental lactate area Obesity independently accounted for 10% of the variance in basal lactate and 11% of the variance in incremental lactate area, neither of which were statistically significant We conclude that elevations in basal lactate are associated with the development of insulin resistance(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin

Controversy regarding defective postprandial thermogenesis in obesity may partly be due to methodological factors such as duration of measurement. To clarify further the role of blunted thermogenesis in obesity, the thermic effect of food was compared in seven lean (mean ± SEM, 15.7% ± 1.5% body fat, by densitometry) and seven obese men (37.3% ± 3% fat) over 3 and 6 hours. The groups were matched for age (35 ± 2 and 33 ± 2 years for the lean and obese groups; range, 25 to 39 years), fat-free mass (FFM), and aerobic fitness. Resting metabolic rate (RMR) was measured by indirect calorimetry for 6 hours on two mornings, in randomized order: (1) after a 720-kcal liquid mixed meal, which was 24% protein, 21% fat, and 55% carbohydrate; and (2) in the postabsorptive state. The thermic effect of food, calculated as postprandial minus postabsorptive RMR, was significantly greater for the lean than obese men for the first 3 hours of measurement (67 ± 6 v 49 ± 3 kcal3 hours; P < .01). During the second 3 hours, the thermic effect of food was marginally, but not significantly, greater for the lean than obese men (34 ± 8 v 20 ± 4 kcal3 hours; P = .10, NS). Over the entire 6 hours, the thermic effect of food was significantly greater for the lean than obese men (100 ± 12 v 69 ± 5 kcal6 hours; P < .05). Three hours after the meal the increment above fasting RMR was greater for the lean than obese men (28% ± 7% v 13% ± 3% above fasting; P < .05). However, 6 hours after the meal the elevation above fasting RMR was not significantly different between the lean (6% ± 3%) and obese men (0% ± 2%). These results indicate that the thermic effect of food is neither delayed nor more prolonged in obese compared with lean men and provide further evidence for defective thermogenesis in obesity.

Maria Bernadette Tomas

Papers

Thermic effect of a meal over 3 and 6 hours in lean and obese men.