Adaptive Mechanisms In GRown up ObeSity Study (AMIGROS)

Inclusion Criteria:

1. Men and women of age: 40.0 - 70.0 years
2. BMI: 18.0 - 25.0 kg/m2 (lean subjects) and BMI 30.0 - 38.0 kg/m2 (Ob-IS and Ob-IR)
3. Fasting insulin < 9.0 mU/l (lean and Ob-IS subjects) and fasting insulin > 9.0 mU/l (Ob-IR)
4. Fasting glucose < 6.1 mmol/l
5. Body temperature < 37.5°C
6. First-degree relative with known T2D in Ob-IR
7. Weight stable ± 5 kg < 3 months before screening
8. Fluent in Swedish and can follow given instructions
9. Consent given to participate

Exclusion Criteria: 10. First-degree relative with known T2D in lean or Ob-IS subjects 11. Alcohol intake > 10 units/week or known high alcohol intake < 10 years back in time 12. Daily use of cigarettes or daily frequent use of smokeless tobacco not enabling theparticipant to suspend nicotine during a visit at the research center without gettingabstinent 13. Regular physical activity corresponding to Saltin-Gimby level 4 14. Special diet eg Atkins or 5:2 for weight reduction. Vegetarian food accepted ifduration > 1 year 15. Impaired fasting glucose (IFG) (venous fasting plasma glucose 6.1-6.9 mmol/l) 16. Type 2 diabetes according to ADA criteria 17. Ongoing or previous ischemic heart disease, eg angina pectoris, unstable angina orprevious myocardial infarction treated with platelet inhibitors or non vitamin-K oralanticoagulants 18. Heart failure (NYHA II-IV) or cardiac arrhytmia that needs medical treatment 19. Previous cerebral infarction or transitory ischemic episodes (TIA) treated withplatelet inhibitors or other anticoagulants 20. Peripheral arterial insufficiency eg claudication 21. Hypertension >170/105 mmHg at screening or more than one class of drugs for treatmentof known hypertension 22. Lipid disorder defined as fasting serum triglycerides > 5.0 mmol/l or serumcholesterol > 7.5 mmol/l 23. Hematologic diseases such as anemia not being substituted (Hb < 130 g/l in males andHv < 120 g/l in females) or disease causing bleeding disorder 24. Renal failure defined as absolute estimated glomerular filtration rate (eGFRcreatinine) < 60 ml/min/1.73 m2 25. Hypothyroidism defined as TSH > 4.0 mIE/l and symptoms 26. Liver disease e.g. hepatitis B, cirrhosis or conditions where AST or ALT are > 2 timesUNL 27. Systemic inflammatory disease e.g. rheumatoid arthritis, ulcerative cholitis or Chronsdisease. Celiac disease, dyspepsia or IBS are excepted 28. Chronic bronchitis or chronic obstructive pulmonary with disease symptoms 29. Previous pancreatitis or other disease in pancreas that needs treatment 30. Migraine elicited by stress 31. Spinal insufficiency causing inconvenience lying in supine position during the studyday 32. Drug addiction interfering with the study procedures 33. Psychiatric insufficiency interfering with the study procedures 34. Medication with potential to affect adipose tissue metabolism that can not be stopped 10 days before the study days 35. Treatment with beta-blockers 36. Less than three months from previous use of antibiotics 37. Cancer disease < 5 years since diagnosis 38. Physical examination or laboratory results indicating that participation in the studyis inappropriate 39. Pregnancy or intention to be pregnant during the study 40. Shift work > 1 time per week that might interfere with the circadian rhytm 41. Other reasons that causes the PI to believe that participation is inappropriate