Subject(s)
Dietary Fats/administration & dosage , Energy Metabolism/physiology , Life Style , Metabolic Syndrome/etiology , Obesity/etiology , Dietary Fats/classification , Dietary Fats/metabolism , Drug Interactions , Energy Intake , Genetic Predisposition to Disease , Humans , Metabolic Syndrome/genetics , Obesity/physiopathologyABSTRACT
ATP-sensitive potassium (KATP) channels are present in many cell types and link cellular metabolism to the membrane potential. These channels are heterooctamers composed of two subunits. The sulfonylurea receptor (SUR) subunits are targets for drugs that are inhibitors or openers of the KATP channels, while the inwardly rectifying K+ (Kir) subunits form the ion channel. Two different SUR genes (SUR1 and SUR2) and two different Kir6.x genes (Kir6.1 and Kir6.2) have been identified. In addition, isoforms of SUR2, SUR2A and SUR2B, have been described. We have previously performed expression profiling on pooled human adipose tissue and found high expression of SUR2. Others have reported expression of SUR1 in human adipocytes. The aim of this study was to characterize the expression of the sulfonylurea receptor complex components in human adipose tissue. RT-PCR analysis, verified by restriction enzyme digestions and DNA sequencing, showed that SUR2B, Kir6.1 and alpha-endosulfine, but not SUR1, SUR2A or Kir6.2, are expressed in human adipose tissue. Real-time RT-PCR showed that SUR2B was expressed at higher levels in subcutaneous compared with omental adipose tissue in paired biopsies obtained from seven obese men (p < 0.05). Analysis of tissue distribution showed that SUR2B expression in adipose tissue was lower than that in muscle, similar to that in heart and liver, while the expression in pancreas was lower. The effect of caloric restriction was tested in obese men (n = 10) treated with very low calorie diet for 16 weeks, followed by a gradual reintroduction of ordinary food for 2 weeks. Biopsies were taken at week 0, 8 and 18. There was no consistent effect of weight reduction on SUR2B or Kir6.1 expression. We conclude that the necessary components for a local sulfonylurea system are expressed in human adipose tissue and that the sulfonylurea receptor complex in this tissue is composed of SUR2B and Kir6.1. The expression of SUR2B was higher in subcutaneous compared with omental adipose tissue and was not affected by weight loss.
Subject(s)
ATP-Binding Cassette Transporters/metabolism , Adipose Tissue/metabolism , Obesity/metabolism , Peptides/metabolism , Potassium Channels, Inwardly Rectifying/metabolism , Potassium Channels/metabolism , Receptors, Drug/metabolism , ATP-Binding Cassette Transporters/genetics , Diet Therapy , Female , Humans , Intercellular Signaling Peptides and Proteins , KATP Channels , Middle Aged , Peptides/genetics , Potassium Channels/genetics , Potassium Channels, Inwardly Rectifying/genetics , Receptors, Drug/genetics , Sulfonylurea Receptors , Weight LossABSTRACT
BACKGROUND: The adipocyte-derived hormone leptin regulates food intake by stimulation of the long leptin receptor isoform in the hypothalamus. The long leptin receptor is also expressed in the piriform cortex, an area involved in the relay of olfactory cues. In rodents, both olfaction and leptin influence food seeking. OBJECTIVE: To examine whether serum leptin levels are associated with olfaction in humans. SUBJECTS: Two distinct samples were analyzed. The population-based sample, 60 men and 61 women, was randomly selected from a population living in Mölndal, Sweden. The obese sample, 31 men and 27 women, was from the ongoing Swedish Obese Subjects (SOS) study. METHODS: Olfactory function was assessed with a two-part test used at Connecticut Chemosensory Clinical Research Center. RESULTS: In the population-based sample, multiple regression analysis revealed a gender difference (interaction gender x leptin; P = .016) between the association of odor identification and logarithmically transformed (log) leptin when adjusting for smoking and log body mass index (BMI). In men the association was positive (beta = 13.2; P = .0026), whereas in women it was negative (beta = -11.4; P = .050). When further adjusting for the influence of menopause and estrogen treatment, the negative association between odor identification and leptin became stronger for women in the population-based sample (beta = -13.7; P = .027). In the obese sample, the associations were similar in direction to those observed in the population-based sample, although nonsignificant. CONCLUSION: Serum leptin levels were associated with odor identification in a randomly selected population. The association was gender-specific and independent of BMI. High odor identification scores were associated with high serum leptin levels in men and low serum leptin levels in women. This provides further support for previously recognized gender differences in the leptin system and suggests alternative ways for leptin to modulate its effects.