Thesis (doctoral)--Universitetet i Lund. / Reprints of journal articles inserted in pocket on back cover.

Thesis (Ph. D.)--University of Wisconsin, 1967. / Typescript. Vita. Includes bibliographical references.

The preadipocyte is crucial for healthy adipose tissue (AT) remodeling, and insulin resistance in these cells may contribute to AT dysfunction. Chronic exposure to insulin and high glucose induces insulin resistance in the 3T3-L1 mouse adipocyte cell line in vitro, however, whether this occurs in human preadipocytes is not known. To investigate this, human preadipocytes were isolated from subcutaneous AT obtained from 6 female patients undergoing elective surgery (Research Ethics Board-approved). Human preadipocytes were incubated in 5 mM glucose or 25 mM glucose in the presence or absence of 0.6 nM insulin for 48 hours, followed by acute 100 nM insulin stimulation. 25 mM glucose + 0.6 nM insulin inhibited insulin-stimulated tyrosine phosphorylation of IR-β (77%) and IRS-1 (81%) compared to NG (p<0.01), however, insulin-stimulated Ser473 Akt phosphorylation was not affected. 25 mM glucose and/or 0.6 nM insulin did not significantly change levels of pro-inflammatory adipokines. 25 mM glucose and/or 0.6 nM, prior to and/or during 14 days of adipogenic induction, did not affect levels of adipogenic markers or intracellular triglyceride accumulation.

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Abstract Background: The discovery of brown adipose tissue (BAT) in adults has sparked interest in its role as a therapeutic target in metabolic disorders. Preliminary studies have indicated that infrared thermography may be a promising way to quantify this thermogenic organ, which in humans is located primarily in the supraclavicular area and is activated by cold. However, ways to standardize infrared thermography methodology and to ensure measurements are reproducible have not been established. Objective: This study aims to establish a standardized and reproducible protocol to measure a thermal response to cold in the supraclavicular area. Method: In phase 1 of the study, thermal images of the supraclavicular area were taken on 3 occasions in 28 healthy adult males with mean age 23.95 ±5.87 years and mean BMI 25.20 ±3.93 kg/m2 who demonstrated a 100kcal/d increase in energy expenditure when exposed to 12ºC; a temperature known to increase BAT activity without shivering. During the first and second visits, participants were acclimated for 1 hour at 32ºC and room temperature (20-23ºC) respectively, followed by a 1 hour period of torso cold exposure at 12ºC using a cooling blanket. The third visit consisted of taking thermal images at room temperature over two hours. Body composition was measured with DEXA scanner. In phase 2, 3 trials of 32ºC acclimation followed by 12ºC cold exposure (32ºC-cold) were studied in 14 healthy adult males (mean age 20.93 ±2.4 years and mean BMI 23.55 ±3.15 kg/m2) for repeatability. The outdoor temperature on the morning of each visit was recorded from the website http://climate.weather.gc.ca in both phases. Results: In phase 1 the supraclavicular temperature stabilized after 45 minutes of acclimation at 32ºC and then rose abruptly with cooling, plateauing at 10 minutes. The change in supraclavicular temperature in response to cooling was greater after 32ºC compared to room temperature acclimation (0.22 ±0.19 vs 0.13±0.17ºC, p=0.053). There was no relation between outdoor temperature on the morning of the visit and the 32°C-cold thermal response (r=-0.18, p=0.14). The 32ºC-cold thermal response did not correlate with cervical and supraclavicular fat in 25 young males with BMI between 19.3-32.3 kg/m2 (r=-0.26, p=0.21). In phase 2, the thermal response after 32ºC acclimation was reproducible [intraclass correlation coefficient of 0.69 (0.14-0.72)]. Conclusion: Acclimation at 32ºC produces a greater and earlier response to cold in the supraclavicular area than room temperature acclimation. The thermal response after 32ºC acclimation is reproducible and unlikely to be affected by outdoor temperature and subcutaneous fat in the neck. These data suggest that the use of infrared thermography using the 32ºC-cold protocol may be effective for detecting the metabolic activity of brown adipose tissue. / Thesis / Master of Science (MSc)

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