Table 1.
Metabolic phenotypes of male and female mice deleted (specifically in adipocytes or global KO) for various sex steroid receptors, enzymes regulating local production of active sex steroids and growth hormone receptor (or over-expressing them) as presented Section 2.3.3 and Section 2.3.4.
| Gene Deleted/Over-Expressed | Metabolic Phenotype in Males | Metabolic Phenotype in Females | Ref. |
|---|---|---|---|
| Sex steroid receptors | |||
| Estrogen receptor (ERα) | |||
| Global KO | Increased body weight and fat mass, insulin resistance and impaired glucose tolerance | Increased body weight and fat mass, insulin resistance and impaired glucose tolerance | [49] |
| Adipose specific deletion | No changes in total body weight but enhanced expression of fibrosis markers and inflammation in the adipose tissues; no changes in glucose tolerance; protective role of ERβ against fibrosis and inflammation when ERα is lacking (although it is less important than in females deleted for ERα in adipocytes | No changes in total body weight but enhanced expression of fibrosis markers and inflammation in the adipose tissues; worsening glucose intolerance despite no change in plasma levels of 17β-estradiol; protective role of ERβ against fibrosis and inflammation when ERα is lacking | [48] |
| Androgen receptor (AR) | |||
| Global AR KO or hepatic-, muscle- or pancreas-specific KO | Obesity with decreased energy expenditure, hepatic steatosis, and insulin resistance | No data | [55] |
| Adipose specific deletion | Do not exhibit obesity or enhanced fatness probably due to increased estradiol levels measured in adipose tissue | No data | [56] |
| Enzymes regulating local production of active sex steroids | |||
| Aromatase (Arom) | |||
| Global KO (ArKO) | ArKO mice grow larger with aging than age-matched wild-type mice and exhibit dramatic expansion of the visceral depot with larger adipocytes | ArKO mice grow larger with aging than age-matched wild-type mice and exhibit dramatic expansion of the visceral depot with larger adipocytes | [57] |
| Overexpression in adipocytes | Reduced inflammation and increased insulin sensitivity of adipose tissue | No data | [32] |
| Steroid sulfatase (STS) | |||
| Overexpression in adipocytes | Worsening of metabolic health, including weight and fat gain, as well as aggravating insulin resistance, which was due to enlarged adipocytes, increased fat inflammation, and dysregulated adipogenesis. These effects were related to increased androgenic activity since castration abolished the effects. | Alleviation of metabolic functions and decreased inflammation in the adipose tissue | [61] |
| Estrogen sulfotransferase (EST) | |||
| Global KO | Worsening of metabolic abnormalities under obesity conditions with highly dysfunctional adipocytes characterized by elevated expression of several macrophage markers and a high density of crown-like structures, all signs of local inflammation. | A metabolic benefit is described related to enhanced estrogenic activity in the liver; no effect on the adipose tissues. | [59] |
| 11β-HSD1 | |||
| Overexpression in adipocytes | Hypertrophy of visceral adipose tissue, insulin resistance, diabetes, dyslipidemia, and hypertension in mice | No data | [64] |
| adipose specific deletion | Reduced visceral fat accumulation; higher expression of PPARγ; lower leptin and resistin levels; increased energy dissipation (UCP2) | No data | [65] |
| Growth hormone receptor (GhR) | |||
| Adipose specific deletion | Improvement of with improved glucose homeostasis and decreased TG levels, inflammation and fibrosis; increased adiposity due to increased cell size in the subcutaneous compartment | Metabolic profile similar to males with subtle differences | [69] |