Target and Drug (candidate) or Knockout | Phenotype | Ref. |
---|---|---|
PPARγ | ||
Rosiglitazone & pioglitazone: | Increased insulin sensitivity with edema and weight gain as side-effects | Aronoff et al., 2000; Phillips et al., 2001; Hussein et al., 2004 |
Systemic knockout | −/−: lethal; impaired placental, cardiac, and adipose tissue development +/−: improved insulin sensitivity | Kubota et al., 1999; Miles et al., 2000; Yamauchi et al., 2001 |
SCD1 | ||
Novartis/Xenon preclinical inhibitor | No published data | |
Systemic knockout | −/−: decreased body fat mass, increased oxygen consumption, increased insulin sensitivity; abnormal skin, eyelid, and hair −/+: lower triglycerides, cholesterol ester, and wax ester levels in eye lids compared to +/+ | Miyazaki et al., 2000; Ntambi et al., 2002 |
DGAT1 | ||
Systemic knockout | −/−: resistance to diet induced obesity, increase metabolic rate; alopecia, impaired mammary gland development −/+: intermediary resistance to diet induced obesity | Smith et al., 2000; Chen et al., 2002; Chen, 2006 |
11β-HSD | ||
Amgen/Biovitrum: AMG 221, phase I | No published data | |
Systemic knockout | −/−: resistance to diet induced obesity, increase metabolic rate −/+: no reported phenotype | Morton et al., 2004 |
PTP-1B | ||
IDD-3848, preclinical ISIS-113715, antisense (phase II) | Increased insulin sensitivity Reduction in HbA1c and fasting glucose | Abstracts only no published data |
Systemic knockout | −/−: resistance to diet induced obesity, improved insulin sensitivity −/+: resistance to diet induced obesity, improved insulin sensitivity | Elchebly et al., 1999; Klaman et al., 2000 |