Adipose tissue is now recognised as a highly active metabolic and endocrine organ. Great strides have been made in uncovering the multiple functions of the adipocyte in cellular and molecular detail, but it is essential to remember that adipose tissue normally operates as a structured whole. Its functions are regulated by multiple external influences such as autonomic nervous system activity, the rate of blood flow and the delivery of a complex mix of substrates and hormones in the plasma. Attempting to understand how all these factors converge and regulate adipose tissue function is a prime example of integrative physiology. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities, including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissues to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. This implies the existence of one (or more) signal(s) to the adipose tissue that reflects the body's energy status, and points once again to the need for an integrative view of adipose tissue function.
SUMMARY Samples of saliva (4 in 24 hours), collected at monthly intervals for the first 6 months of life in 8 term infants by their mothers, were analysed for cortisol by radioimmunoassay. Values in the first month were more variable, daily mean values were greater, and amplitudes of variation were greater than in subsequent months. The circadian rhythm appeared by the third month.The age at which the 'adult' circadian rhythm of cortisol secretion emerges is difficult to ascertain for obvious ethical reasons and the few data available all conflicting. Franks' measured plasma 1 7-hydroxycorticosteroids at 8 am and 8 pm in children and concluded that the 'adult' pattern emerged between 1 and 3 years. A study, however, based on urine collections every 3 hours throughout the day in male infants suggested a diurnal rhythm of excretion of 17-hydroxycorticosteroids by day 26 of life.2 The most complete study, by Zurbrugg,3 who took blood samples every 4 hours from 6 neonates (3-9 days old), from S infants (1-6 months old), and from 11 children (1j-1 1 J years old), concluded that 12 hourly cycles of plasma cortisol occurred in the neonatal period and a 24 hour cycle in the second year of life. The mean daily plasma cortisol concentration and mean amplitudes of variation were comparable in all age groups.Mixed salivary cortisol values closely reflect plasma free cortisol values4 and a circadian rhythm has been identified in adults5 6 and children.7 To determine when the circadian rhythm appeared an ethically acceptable longitudinal study was carried out in 8 normal infants in their homes, using small salivary samples taken by mothers for cortisol estimation. Patients and methodsEight term neonates (4 boys and 4 girls), whose mothers agreed to participate in the study, were selected. Four deliveries were unassisted, 1 was forceps assisted, and 3 were by caesarian section.All babies were of normal birthweight (2.95-3.5 kg) except 1 who was light for gestational age (2 3 kg at 41 weeks). Nonie ofthe babies had postnatal problems and all were well during the study. Five were breast fed. Mothers were asked at what age the night feed was omitted and babies slept throughout the night.Saliva collection. Mothers were requested to provide 4 samples in a 24 hour period during weeks 1,4,8, 12, 16,20, and 24 of life. Several collections requested for week 24 were made between weeks 24 and 30. The first sample was requested at a convenient time between 6 am and 8 am, the second between 11 am and 1 pm, the third between 3 pm and 6 pm, and the final sample between 10 pm and 12 pm. Mothers were instructed to place a small citric acid crystal on the infant's tongue and aspirate 1-3 ml of saliva with a disposable mucus extractor over the next few minutes.8 Saliva was transferred to small plastic capped bottles (with the times recorded) that were sent to the laboratory on the following day and stored at -20°C until analysed.The project was approved by the local ethical committee. On consultation during and after the study mothers did not ...
Fatty acid desaturases such as steaoryl-CoA desaturase (SCD) convert saturated to unsaturated fatty acids and are involved in lipogenesis. Observational and animal data suggest that SCD-1 activity is related to insulin sensitivity. However, the effects of insulin-sensitizing drugs on SCD gene expression and desaturase activities are unknown in humans. In a randomized, placebo-controlled, double-blind, crossover study, 24 subjects with type 2 diabetes and one subject with partial lipodystrophy and diabetes due to dominant-negative mutation in the peroxisome proliferator-activated receptor-␥ (PPAR␥) gene (P467L) received placebo and rosiglitazone for 3 months. SCD gene expression in adipose tissue was determined in 23 subjects, and in a representative subgroup (n ؍ 10) we assessed fatty acid composition in fasting plasma triglycerides to estimate SCD and ⌬6-and ⌬5-desaturase activity, using product-to-precursor indexes. SCD mRNA expression increased by 48% after rosiglitazone (P < 0.01). SCD and ⌬5-desaturase but not ⌬6-desaturase activity indexes were increased after rosiglitazone versus placebo (P < 0.01 and P < 0.05, respectively). The change in activity index but not the expression of SCD was associated with improved insulin sensitivity (r ؍ 0.73, P < 0.05). In the P467L PPAR␥ carrier, SCD and ⌬5-desaturase activity indexes were exceptionally low but were restored (52-and 15-fold increases, respectively) after rosiglitazone treatment. This study shows for the first time that rosiglitazone increases SCD activity indexes and gene expression in humans. An increased SCD activity index may reflect increased lipogenesis and might contribute to insulin sensitization by rosiglitazone. The restored SCD activity index after rosiglitazone in PPAR␥ mutation supports a pivotal role of PPAR␥ function in SCD regulation. Diabetes 54:1379 -1384, 2005 P lasma fatty acid composition has been closely related to insulin resistance in epidemiological studies (1). Recently it was shown that the palmitic acid (16:0) content of plasma triglycerides was independently associated with factors related to insulin resistance (2). These associations can be partly explained by dietary fat intake but also by the endogenous activities of the desaturases involved in fatty acid biosynthesis (3). Desaturase activities are known to be regulated by genetic and hormonal factors that are independent of diet and fat intake (4).In several (5,6), but not all (7), cross-sectional studies, insulin resistance has been associated with increased indexes of ⌬9-desaturase (steaoryl-CoA desaturase [SCD]) and ⌬6-desaturase activities and decreased ⌬5-desaturase activity. This would be in line with the findings from the study of SCD-1-deficient mice (8).SCD is the key enzyme in the biosynthesis of monounsaturated fatty acids from saturated fatty acids (i.e., the final step in lipogenesis) (4), and the palmitoleic/palmitic acid (16:1/16:0) index (also known as the "desaturation index") (9) can be used to estimate SCD activity (5,9). However, our knowledge in hu...
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