Person:

Hamnvik, Ole-Petter

Objective: To study the day-night variation of omentin-1 levels and assess whether leptin, and/or short-and long-term energy deprivation alter circulating omentin-1 levels via cytokines. Design and Methods Omentin-1 levels were measured hourly in serum samples from six healthy men to evaluate for day-night variation. To study effects of acute energy deprivation and of leptin administration, eight healthy subjects were studied in the fasting state for 72 hours with administration of either placebo or metreleptin in physiological replacement doses. We evaluated the effect of leptin in pharmacological doses on serum omentin-1 and cytokine levels, as well as on omentin-1 levels in ex vivo omental adipose tissue, in fifteen healthy volunteers. To study the effect of chronic energy deprivation and weight loss on omentin-1 levels we followed eighteen obese subjects for 12 months who underwent bariatric surgery. Results: There is no day-night variation in omentin-1 levels. Short-term and chronic energy deprivation as well as ex vivo leptin administration and physiological replacement doses of leptin do not alter omentin-1 levels, whereas pharmacologic doses of metreleptin reduce omentin-1 levels whereas levels of TNF-α receptor II and IL-6 tend to increase. Conclusions: Omentin-1 levels are reduced by pharmacological doses of metreleptin independent of effects on cytokine levels.

Background/Objectives: Obesity is characterized by chronic inflammation and immune dysregulation, as well as insulin resistance, but the link between obesity and adaptive immunity remains to be fully studied. Methods: To elucidate the role of adaptive immunity on body composition, glucose homeostasis, and inflammation, recombination-activating gene 1 knockout (Rag1-/-) mice, without mature T lymphocytes or B-lymphocytes, were maintained on a low (LFD) or high fat diet (HFD) for 11 weeks. Results: Rag1-/- mice fed HFD gained significantly more weight and had increased body fat compared to wild type. Downregulation of energy expenditure as well as brown fat UCP-1 and UCP-3 gene expression were noticed in HFD fed Rag1-/- mice compared to LFD. HFD mice had significantly decreased energy intake compared to LFD mice, consistent with decreased AgRP and increased POMC gene expressions in the hypothalamus. Moreover, compared to wild type, Rag1-/- mice had lower IL-4 levels, a cytokine recently found to induce browning in white adipocytes, and higher IL-12 levels in HFD fed Rag1-/- mice. Despite that HFD Rag1-/- mice were more obese, they had similar glucose, insulin, and adiponectin levels, while leptin was marginally increased. Conclusions: Mice with deficiency in adaptive immunity are obese, partly due to decreased energy expenditure, but are metabolically normal, suggesting that mature lymphocytes play necessary roles in the development of obesity-related metabolic dysregulation.